HCV Infection Eradication in Cirrhosis With and Without Portal Hypertension

Atif Zaman, MD, MPH reviewing Di Marco V et al. Gastroenterology 2016 Jul. Successful treatment was associated with reduced risks for liver complications, hepatocellular carcinoma, and death, but not progression of portal hypertension. Hepatitis C virus (HCV) infection eradication in patients with cirrhosis may change the course of liver disease outcomes. Few data exist regarding the effect of HCV infection eradication on portal hypertension in this population. In a prospective cohort study performed at a single tertiary care center in Italy, researchers assessed liver-related outcomes including ascites, variceal hemorrhage, encephalopathy, hepatocellular carcinoma, and deaths in 444 patients with compensated, HCV-related cirrhosis with or without small esophageal varices. Patients underwent treatment with peginterferon and ribavirin for 48 weeks. During endoscopic screening and surveillance, the development of new varices and progression of varices were assessed. During a median follow-up of 7.6 years, the following results were observed: Sustained virologic response (SVR) at 24 weeks posttherapy was achieved in 31% of patients without varices and 18% of those with varices. Among patients without varices, achieving SVR was significantly associated with lower likelihood of developing varices (hazard ratio, 0.2). Among patients with varices, achieving SVR was not significantly associated with reduced risk for progression of varices. Regardless of whether patients had varices, achieving SVR was associated with reduced risks for liver disease complications (e.g., ascites), hepatocellular carcinoma, and mortality.

Half at Night and Half in the Morning—a Better Way To Prepare for Colonoscopies

Gastroenterologists and other physicians are virtually unanimous in appreciating the vital importance of colonoscopy screenings. In preparation for colonoscopies, we direct patients to drink a large volume of bowel-cleansing liquid, usually in one day. Past studies have shown that splitting this dose—drinking half the night before and half in the morning before the procedure—leads to better bowel cleansing compared with drinking the entire dose the night before. Yet barriers still remain to the acceptance of split dosing, including the perceived patient inconvenience of consuming two separate doses. My colleagues and I wanted to learn whether the split-dose preparation is more convenient for patients, and whether it would lead to finding more precancerous polyps. Split dosing is already recommended by the U.S. Multi-Society Task-Force on Colorectal Cancer, and our study provides additional support for its benefits by demonstrating that it decreases total bowel prep ingestion time, reduces the intensity and duration of bowel movements, and is associated with less sleep disruption. The results were clear to us in confirming the superior performance of the split dose, not only in overall bowel cleansing, but in detecting dangerous polyps. Our team, including Carol Burke, MD, found that endoscopists reported “excellent” or “good” cleansing in 95.6% of the split-dose group, a full 10 percentage points above the single-dose group, which achieved those ratings in only 85.5% of cases. The split-dose method also resulted in a higher overall rate of finding polyps and adenomas. However, the most dramatic difference was specifically seen in detecting another serious and potentially life-threatening condition—the presence of sessile serrated polyps (SSPs). In screening patients from both groups, the physicians found SSPs at a rate four times higher in the split-dose group than in the single-dose group (9.9% vs. 2.4%). We regard our results as additional evidence for practitioners to confidently adopt split dosing as a standard procedure. For patients who aren’t given this option, we recommend they ask their GI about it. The improved ability to detect SSPs is too significant a benefit to overlook in our continuing effort to eliminate colorectal cancer. Nicholas Horton, MD, is a PGY-2 resident in internal medicine at the Cleveland Clinic. He completed medical school at the Wright State University Boonshoft School of Medicine, in Dayton, Ohio. He plans to pursue a fellowship in gastroenterology, and has a particular academic interest in colorectal cancer prevention and inflammatory bowel disease. Dr. Horton presented data from this study, “Sessile Serrated Polyps Are Detected More Often With Split Versus Single Dose Low Volume Bowel Preparation: Results From a Prospective Trial,” at the 2016 Digestive Disease Week (abstract Su1663). The study received outside funding from Salix Pharmaceuticals.

Brief Talk Gets Patients in Control of Reflux

Ninety seconds of education appeared to work wonders in getting heartburn patients to optimize their use of the proton pump inhibitor omeprazole, researchers reported here at the annual Digestive Disease Week conference. Patients who were given instruction in the medicine's use by their doctor had a mean 4-point drop in Gastroesophageal Reflux Disease Symptom Assessment Scale Mean Symptom Score after 6 weeks compared with just minor change among patients who were not given the educational talk (P<0.01), said Abhijeet Waghray, MD, of MetroHealth System/Case Western Reserve University in Cleveland. Similarly, significant declines in symptom frequency and symptom severity were seen among those patients who had the intervention, Waghray said at his poster presentation. And what was the intervention that produced these results? Patients were told they they had to take their medication 15 to 30 minutes before their first meal of the day in order for omeprazole to be effective. "It takes about 90 seconds to deliver the message and answer any questions," he told MedPage Today. In so-called OSCAR (Omeprazole Dosing and Symptom Control -- A Randomized Controlled Trial), 29 patients were given the quick educational lesson when they came to the office and complained that their treatment wasn't effective; 35 other patients were controls -- they where not provided with emphasis on how to take their medicine, but rather were essentially waitlisted to receive the talk a few weeks later. In the meantime, they were encouraged simply to keep taking omeprazole. Patients were eligible for the study if their experienced heartburn three or more times a week despite treatment with 20 mg omeprazole. They were observed for 2 weeks on the current regimen and then were randomized to received the pep talk on optimal dosing time or were left to continue their medication as they were taking it. Their dose was not changed, although people who were on different doses were not included in the study, Waghray said, to reduce the variables in conducting the research. Four weeks later their symptoms were analyzed. Those given the added instruction achieved an overall significant decrease in symptoms, reflected in reductions in both symptom severity and symptom frequency, Waghray said. After the 6-week trial, the patients who were not given instruction in the first round were provided the educational talk. Symptom assessment at 4 weeks showed reductions similar to those achieved in the first intervention group. About 40% of the patients in the study were men; about 37.5% were Caucasian and 48.4% were African. More than 40% of the patient population had attended college or were college graduates or had done post-graduate studies. Waghray said there were no statistically significant differences between the groups' demographics. "Proper education and proton pump inhibitor dosing should serve to reduce the burden of persistent GERD symptoms and related costs of uncontrolled disease," Waghray said. William Ravich, MD, of Johns Hopkins University, told MedPage Today, "It is absolutely true that people come in and are not taking their medication at the appropriate time. This has been the standard time for taking these drugs since they were introduced decades ago. Either doctors don't pay enough attention to educating the patient or the patient ignores it. "It is very difficult to take medication a half hour before breakfast," said Ravich, who was not involved with the study. "I have trouble taking medicine on any regular schedules. So I think this has to be reinforced, and I think this study justifies the original recommendations for taking the drugs."

Hospitals Struggle to Keep Endoscopy Safe

Hospitals are taking the problem of gastrointestinal endoscope reprocessing seriously, reports here at Digestive Disease Week suggested, to the point of spending hundreds of thousands of dollars in order to meet recent FDA guidelines. Reports last year that dozens of patients had been sickened -- some fatally -- by multidrug-resistant infections they acquired from incompletely sterilized duodenoscopes and other endoscopy instruments have prompted an industry-wide effort to do a better job of cleaning the equipment after use. In August, after it was revealed that the manufacturers had received numerous reports of carbapenem-resistant enterobacterial (CRE) infections over a multiyear period without doing anything about them, the agency issued new guidelines that called on endoscopy centers to rigorously follow manufacturers' instructions for reprocessing and to perform "microbiological culturing on a regular basis" to check on the devices' sterility after cleaning. "Every center that does endoscopy is looking at the quality of their reprocessing and putting in a surveillance program," said John Vargo, MD, MPH, of the Cleveland Clinic, at a DDW press briefing. However, as gastroenterology fellow Ji Young Bang, MD, of Indiana University in Indianapolis, told MedPage Today, the guidelines did not specify how often the culturing should be performed and on what percentage of scopes at any given time. As a result, centers have had to decide for themselves how to follow the letter and spirit of the guidelines without going broke. In many cases, endoscopists are going beyond the manufacturers' recommended reprocessing steps to add their own extra procedures. At Maine Medical Center in Portland, for example, the hospital's Pancreaticobiliary Center has been applying an alcohol "flush and flex" protocol prior to each use -- this in addition to the standard post-use processing. At DDW, Matthew Warndorf, MD, and colleagues reported that they had experienced no endoscope-associated infections after instituting the protocol in mid-2015, during which nearly 1,800 endoscopies involving elevator-equipped instruments were performed. Bang's center simply doubled up on the manufacturers' instructions, performing the entire process twice for every instrument after use. But at both centers, and others that reported culture findings here, none of the beefed-up protocols was 100% effective at sterilizing all scopes every time. Bang, for example, said that 592 culture studies performed on 62 different scopes revealed 59 instances of residual contamination. Although 54 of these were benign organisms, that still left five with pathogenic organisms identified, including three involving enterococci. All of these were found from swabs of the elevator mechanism, a moving part at the endoscope tip that allows the operator to change the working angle of some accessory that appears to be the crux of the contamination problem. "The design of the scopes make it difficult to clean them," said Grace Elta, MD, DDW council chair and a gastroenterologist at the University of Michigan. An FDA advisory panel last year agreed that the current generation of duodenoscopes are all unsafe, but also irreplaceable and therefore must continue to be used. The panel's recommendations on more rigorous adherence to sterilization procedures were largely reflected in the August guidance. Manufacturers' instructions generally call for the endoscope and elevator to be scrubbed with a special brush before liquid and/or gaseous sterilizers are applied. But the elevator mechanism is hinged and has other tiny crevices that appear capable of defeating all mechanical and chemical cleaners. However, said Elta, "historically the endoscope infections have related to human error. ... What most centers are doing is doing their best to eliminate that human error." This can be costly. Bang said that, because the culturing procedure means that a scope must be removed from service until it is certified contaminant-free, her center had to buy 40 new scopes in order to maintain procedure volume, at approximately $10,000 apiece. Douglas Faigel, MD, and colleagues at the Mayo Clinic in Scottsdale, Ariz., reported that they had to buy five new scopes with a list price of $223,000, and three of the unit's instruments ended up with "critical damage" from ethylene oxide gas sterilization. Meanwhile, University of Pennsylvania researchers reported that the direct costs of the culturing program amounted to a little more than $21,000 per year, although that was just for 19 duodenoscopes, each of which was cultured monthly. They did not say anything about new equipment. As for more definitive solutions, everyone asked by MedPage Today said the scope designs need to be made simpler and crevice-free. Vargo said he thought that scopes that need elevator mechanisms would eventually come with "a detachable tip that will allow cleaning." Other approaches might include removable sheaths that keep bacteria from lodging in the scope tip in the first place. An affordable single-use device would be another possibility. Manufacturers haven't publicly reported any such developments yet, Vargo said, but "I suspect in the next couple years we will see some."

Oral recombinant H. pylori vaccine

In a randomized phase 3 trial, 4464 H. pylori uninfected children (ages 6 to 15 years) were assigned to a three-dose oral recombinant H. pylori vaccine or placebo]. At one year, the incidence of H. pylori infection was significantly lower in the vaccine group. Among patients who completed extended follow-up, H. pylori acquisition continued to be lower in vaccinated as compared with unvaccinated children, but protection levels were lower in the second and third year. There were no serious adverse events related to the vaccine. Additional studies with long-term follow-up are needed to validate these results

Skin disorders associated with TNF inhibitor use

A variety of skin disorders have been reported in association with the use of tumor necrosis factor (TNF) inhibitors for inflammatory and autoimmune conditions. The largest of several recent studies of patients with inflammatory bowel disease (IBD) receiving these agents involved a cohort of 917 consecutive patients with IBD on TNF inhibitors for a median of 3.5 years, in whom 29 percent developed skin lesions (12.4 per 100 patient-years) . Specific cutaneous lesions included (from most to least common) psoriasiform eczema, eczema, xerosis cutis, palmoplantar pustulosis, and psoriasis; other abnormalities were mostly infectious and inflammatory skin lesions and alopecia. The majority of patients were managed without discontinuation of TNF inhibitor therapy. Limitations of the analysis included uncertainty regarding the relative roles of the treatment and the underlying disease due to the lack of a matched control group not receiving TNF inhibitors

Olmesartan enteropathy

Olmesartan, an angiotensin receptor blocker (ARB), can produce a "sprue-like enteropathy" characterized by severe chronic diarrhea and weight loss, occurring months to years after initiation of the drug. The largest experience comes from a French cohort of over 4 million patients who initiated therapy with olmesartan, a different ARB, or an angiotensin converting enzyme (ACE) inhibitor . Compared with users of ACE inhibitors, intestinal malabsorption severe enough to cause hospitalization occurred substantially more often among patients taking olmesartan for one to two years (adjusted risk ratio 3.7) and among those taking olmesartan for more than two years (adjusted risk ratio 10.6). Risk was not increased in users of other ARBs. Although a large number of patients (ie, 12,550) needed to be treated with olmesartan for two or more years to produce one additional case of enteropathy requiring hospitalization, less severe but still clinically significant cases of enteropathy may have been more frequent. Patients starting olmesartan should be cautioned about the possibility of developing diarrhea and weight loss. The drug should be stopped if these symptoms occur and another cause is not identified.

Sigmoid resection versus laparoscopic lavage for perforated diverticulitis

The laparoscopic lavage and drainage procedure was introduced as a potentially less morbid alternative to sigmoid resection for patients with perforated diverticulitis. In the SCANDIV trial, 199 patients with perforated diverticulitis were randomized to undergo either laparoscopic lavage or sigmoid resection . At 90 days, laparoscopic lavage did not improve mortality rates (14 versus 12 percent) or major morbidity rates (31 versus 26 percent) compared with sigmoid resection. Furthermore, patients who underwent laparoscopic lavage were more likely to require reoperation (20 versus 6 percent) for complications such as secondary peritonitis or missed sigmoid cancer. Based upon these results and other available data, sigmoid resection with or without fecal diversion remains the preferred intervention for patients with perforated diverticulitis.

Office Visits Prior to Screening Colonoscopy Add to Medical Costs

Office visits prior to screening colonoscopy add to medical costs, and it's unclear whether those visits are necessary, researchers report. "Going into the project, I was expecting there to be more precolonoscopy office visits than we found," Dr. Kevin R. Riggs, from Johns Hopkins University School of Medicine, Baltimore, told Reuters Health by email. "It seems that not having a precolonoscopy office visit (open-access colonoscopy) really is the norm." Open-access colonoscopy began in the 1990s, but how widespread it is has been unclear. Dr. Riggs's team used data from MarketScan Commercial Claims and Encounters to determine the proportion of colonoscopies for colon cancer screening and polyp surveillance that were preceded by office visits and the payments associated with those visits. Among 842,849 patients who underwent colonoscopy between 2010 and 2013, 29.4% had a precolonoscopy visit, according to the February 2 JAMA online report. Among patients with office visits, two-thirds (66.4%) had no significant medical conditions, with a Charlson Comorbidity Index (CCI) of 0, but patients with office visits did have higher CCI than those without office visits. Distributed across all patients, the precolonoscopy office visits added a mean of $36.37 per colonoscopy. While this amount seems modest, it amounts to significant cumulative costs when considering the estimated 7 million screening colonoscopies performed annually in the U.S., the authors point out. The researchers were unable to determine the exact circumstances of these office visits, and they could not determine whether the visits were necessary or appropriate. "Colonoscopy is generally a very safe procedure, and it is unlikely that an office visit with the gastroenterologist beforehand makes it any safer," Dr. Riggs said. "It's possible that the office visit is an opportunity to identify patients who should not undergo colonoscopy because the risk is too high, but that is relative and depends on how much benefit can be expected." "In general, the appropriateness for colonoscopy can be made by primary care doctors, and most patients for whom colon cancer screening is recommended by practice guidelines probably don't benefit from an extra precolonoscopy office visit," he said. "Obviously, if patients don't have a primary care doctor and haven't seen a doctor recently, it's probably a good idea to get checked out before any procedure." "Open-access colonoscopy for colon cancer screening is the norm," Dr. Riggs concluded. "If gastroenterologists aren't offering it, or if primary care doctors are routinely referring their patients for whom they have decided colonoscopy is indicated for evaluation before the colonoscopy, they should consider changing their practice. Not only do these office visits waste potentially hundreds of millions of dollars annually, but requiring unnecessary office visits makes for a less pleasant patient experience." Dr. John I. Allen, clinical chief of digestive diseases at Yale University, New Haven, Connecticut, told Reuters Health by email, "I have worked for 25 years within a large private single specialty (gastrointestinal) group where 85% of endoscopy was open access and 15% was generated after a clinic visit with us. This not only saved money, but freed up clinic to see more needy patients. The no-show rate for endoscopy was 1%." "I now work at Yale - mostly a Medicaid, Marketplace, or Medicare population - where our no-show rate is >20%. Pre-endoscopy visits would be a great addition, but we are so understaffed that it would be impossible," he said. "Open access saves money and is appropriate for a population that complies with recommendations (can follow the complex process of preparation) and will show up for their appointment," Dr. Allen concluded. "Precolonoscopy visits can help prevent canceled procedures due to poor prep (up to 15% of procedures in some populations), identify patients needing more intense care, and in some cases help patients be comfortable with undergoing an invasive procedure." The National Institutes of Health supports two coauthors. One coauthor owns stock in the Advisory Board Company. JAMA 2016

HCV Guideline Update: Treat All Patients With New Drugs

The American Association for the Study for Liver Diseases and the Infectious Disease Society of America (IDSA) have updated HCVguidelines.org so that it reflects the current understanding that virtually all individuals who are positive for the hepatitis C virus (HCV) should receive the newer HCV treatment. The site emphasizes that new sections have been added and that the recommendations are updated regularly as new information becomes available. The guidelines begin by explaining that new direct-acting oral agents that can cure HCV infection have been approved in the United States. "We've been accumulating understanding of the value and safety of the medications," David L. Thomas, MD, MPH, spokesperson for IDSA, explained to Medscape Medical News. He described the change in position as an "evolution." When the newer HCV drugs were first introduced, physicians had to rely entirely on data from clinical trials. The new guidelines reflect the addition of real-world physician experience. The new guidance explains that the sustained virologic response that is characteristic of a successful HCV treatment would benefit almost everyone who is infected with HCV. Moreover, many of the highest-risk patients have already had the opportunity to receive treatment with the new medications. The IDSA notes that the cost of the new drugs and regional availability of the appropriate healthcare provider may still translate into a need to prioritize patients for treatment. Some general practitioners will feel comfortable treating their HCV-positive patients, and others will feel more comfortable referring their patients to a specialist for treatment. "A good relationship between physician and patient is crucial to achieving the best outcomes with direct-acting therapies. The physician needs to make an assessment of a patient's understanding of the treatment goals and provide education on the importance of adherence to the therapy and follow-up care," said IDSA panel cochair Gary Davis, MD, in a press release. Dr Thomas said that although the guidelines are meant to demystify treatment, the most severely affected patients should probably be referred to a specialist. "For hepatitis C, the patients who are often in need of referral are those with severe liver disease and cirrhosis," he explained. Unfortunately, it is hard for physicians to predict reimbursement from insurance companies. "Our focus is on the physicians and the patients," explained Dr Thomas, calling the world of insurance companies "challenging" and "vexing." According to HCVguidelines.org, approximately 3 to 4 million individuals in the United States are chronically infected with HCV, and half of them are unaware of their status.

New onset of grave’s disease during anti-tnfα treatment in a case of fistulizing crohn’s disease

 New onset of grave’s disease during anti-tnfα treatment in a case of fistulizing crohn’s disease Presenting Author: NAWAF ZAKARY
Additional Authors: ALGUILI ELSHEIKH, NOOF HAMID, OMAR ABDULAAL, MOHAMMED ALGHAMDI, WALID FARAH
Corresponding Author: NAWAF ZAKARY
Affiliations: King Fahad Military Medical Complex
The association between inflammatory bowel disease in form of ulcerative colitis and autoimmune thyroid disease has been well documented. However, the association between crohn’s disease and autoimmune thyroid disease is not well established and there have only been a few reported cases in the literature.
Case presentation We present here a rare case of a 35-year-old Saudi female with simultaneous onset of Graves’ disease and fistulizing Crohn’s disease. Crohn’s disease was complicated with intra-abdominal fistulas. Despite intense medical treatment with regular Azathioprine, total parenteral nutrition, antibiotics, and corticosteroids the clinical course of the disease was suboptimal. Finally, the patient underwent laparotomy and right hemi-colectomy with ileo-transverse anastomosis, simultaneous drainage of the abdominal abscess and closure of the opening. Although the surgical approach cured the perforating complications of the disease (fistulas and abscess), the luminal disease in the colon remnant was still active. The subsequent successful treatment with infliximab, azathioprine and mesalazine resulted in the induction and maintenance of the disease remission. Later on, patient develop full blown picture of Graves’ disease after she started infliximab which was stopped later and the patient improved on antithyroid medication. Conclusion: We are not sure whether the association between Crohn’s disease and Gravés disease is infliximab dependent or independent and it needs more case studies and research.
 KeyWord(s): 1. Gravés disease; 2. Crohn’s disease; 3. ulcerative colitis; 4. infliximab; 5. azathioprine
 Poster 136 Journal of Gastroenterology and Hepatology 2014; 29 (Suppl. 3): 51–313 © 2014

Management of iatrogenic esophageal perforation with endoscopic stenting

Management of iatrogenic esophageal perforation with endoscopic stenting
Presenting Author: NAWAF ZAKARY
Additional Authors: ALGUILI ELSHEIKH, NOOF HAMID, HIND HAMID, MOHAMMED ALGHAMDI, WALID FARAH
Corresponding Author: NAWAF ZAKARY
Affiliations: King Fahad Military Medical Complex

Objective: Esophageal perforation is a challenging disease process with high morbidity and mortality. Despite the availability of diagnostic radiological tools, there is still a chance of delaying in diagnosis, because of non specific symptoms. In clinical practice 60% of cases are iatrogenic due to endoscopic procedures. The morbidity and mortality rate is directly related to the delay in diagnosis and initiation of optimum treatment. The reported mortality from treated esophageal perforation is 10% to 25%, when therapy is initiated within 24 hours of perforation, but it could rise up to 40% to 60% when the treatment is delayed beyond 48 hours.

Case Presentation: We like to present a 67 year old female patient of achalasia. She presented with weight loss and progressive dysphagia. Barium swallow and gastroscopy confirmed the diagnosis. She underwent successful first session of endoscopic pneumatic dilation but after the second session, she developed shortness of breath and abdominal pain. Gastrographin studies and computer tomography scan of the chest and abdomen confirmed the diagnosis of esophageal perforation. She was managed conservatively with endoscopic stenting, to which she recovered fully.

Conclusion: Esophageal perforation is a highly morbid condition with high mortality. More accurate diagnosis and less-invasive treatment are reducing morbidity and mortality to more acceptable levels. While surgery remains the gold standard treatment, less invasive and endoscopic methods are being explored, and their role is evolving. For optimum outcome for management of esophageal perforations, a multidisciplinary approach is needed.

Key Word(s): 1. achalasia; 2. esophageal perforation; 3. esophageal stenting

© 2014 The Authors. Journal of Gastroenterology and Hepatology

New onset of grave’s disease during anti-tnfα treatment in a case of fistulizing crohn’s disease

IBD P-254 New onset of grave’s disease during anti-tnfα treatment in a case of fistulizing crohn’s disease Presenting Author: NAWAF ZAKARY Additional Authors: ALGUILI ELSHEIKH, NOOF HAMID, OMAR ABDULAAL, MOHAMMED ALGHAMDI, WALID FARAH Corresponding Author: NAWAF ZAKARY Affiliations: King Fahad Military Medical Complex, King Fahad Military Medical Complex, King Fahad Military Medical Complex, King Fahad Military Medical Complex, King Fahad Military Medical Complex Objective: The association between inflammatory bowel disease in form of ulcerative colitis and autoimmune thyroid disease has been well documented. However, the association between crohn’s disease and autoimmune thyroid disease is not well established and there have only been a few reported cases in the literature. Case presentation We present here a rare case of a 35-year-old Saudi female with simultaneous onset of Graves’ disease and fistulizing Crohn’s disease. Crohn’s disease was complicated with intra-abdominal fistulas. Despite intense medical treatment with regular Azathioprine, total parenteral nutrition, antibiotics, and corticosteroids the clinical course of the disease was suboptimal. Finally, the patient underwent laparotomy and right hemi-colectomy with ileo-transverse anastomosis, simultaneous drainage of the abdominal abscess and closure of the opening. Although the surgical approach cured the perforating complications of the disease (fistulas and abscess), the luminal disease in the colon remnant was still active. The subsequent successful treatment with infliximab, azathioprine and mesalazine resulted in the induction and maintenance of the disease remission. Later on, patient develop full blown picture of Graves’ disease after she started infliximab which was stopped later and the patient improved on antithyroid medication. Conclusion: We are not sure whether the association between Crohn’s disease and Gravés disease is infliximab dependent or independent and it needs more case studies and research. KeyWord(s): 1. Gravés disease; 2. Crohn’s disease; 3. ulcerative colitis; 4. infliximab; 5. azathioprine Poster 136 Journal of Gastroenterology and Hepatology 2014; 29 (Suppl. 3): 51–313 © 2014

Link between early exposure to acetaminophen and childhood asthma found weak, overstated

FROM THE ARCHIVES OF DISEASE IN CHILDHOOD The reported link between early life exposure to acetaminophen and the development of asthma in children is “weak” and “overstated” based on currently available evidence, according to a report published by the Archives of Disease in Childhood. In a review of currently available data culled from Embase and PubMed databases, 1,192 relevant studies conducted between 1967 and 2013 were analyzed, of which 11 were included for analysis. Of these 11 studies, 5 found “increased odds” that exposure to acetaminophen during the first trimester of pregnancy could lead to development of asthma (pooled odds ratio, 1.39); however, there was a high degree of between-study heterogeneity among the trials (I= 64.2%, P = .03), reported Dr. M. Cheelo of the University of Melbourne, and associates. Of those five, only two studies examined the effects of acetaminophen exposure during the second trimester, but attained widely disparate results: Study one reported an OR of 1.06, while the other reported an OR of 2.15, with I= 80%. Two studies also tested acetaminophen exposure during the third trimester and found a “weak association,” with a pooled OR of 1.17. Three studies look at acetaminophen exposure through an entire pregnancy, but all had “significant heterogeneity” in their findings (OR = 1.65, 1.22, and 0.74; I= 89%). Only one study that was examined adjusted for respiratory tract infections during pregnancy, but according to the authors, “all studies that adjusted for early life respiratory tract infections found a reduction in the association between [acetaminophen] exposure and subsequent childhood asthma” (Arch. Dis. Child. 2014 [doi:10.1136/archdischild-2012-303043]). The other 6 of the 11 total studies examined acetaminophen exposure over the first 2 years of life. Three of these studies found a “weak positive association,” as did four studies directly comparing children with and without acetaminophen exposure. All but one study adjusted results for respiratory tract infections during pregnancy, which caused a “moderate attenuation of the association between frequency of [acetaminophen] intake and childhood asthma.” Consequently, investigators concluded that “evidence of an association between early life [acetaminophen] and asthma is often overstated, and there is currently insufficient evidence to support changing guidelines in the use of this medicine.”

PPI, steroid use raises risk of CDAD recurrence

AUSTIN, TEX. (FRONTLINE MEDICAL NEWS) – Use of proton pump inhibitors and steroids was independently associated with recurrences of Clostridium difficile–associated diarrhea among patients in an intensive care unit, based on a retrospective chart review reported at the annual meeting of the American College of Chest Physicians. Recurrences were noted in 268 of 2,019 patients who were admitted to a single intensive care unit during a 6-year period and were initially treated successfully for C. difficile–associated diarrhea (CDAD). In a univariate analysis, recurrence was correlated with use of proton pump inhibitors (PPIs) and steroids, but not with age, male gender, or length of hospital stay. After adjusting for age, sex, length of stay, and treatment used, the relationships between recurrence and PPI and steroid use remained statistically significant (P = .0331 and P = .0305, respectively), Dr. Ala Nijim of Akron (Ohio) General Medical Center. The study subjects comprised 798 men and 1,221 women with an average age of 68 years and an average hospital length of stay of 10 days. Severe disease was present in 233 patients, and 51 had cancer. CDAD in this study was defined as at least three episodes of loose stools in less than 24 hours with a positive C. difficile toxin assay. Recurrence was defined as a second positive stool test within 90 days following complete resolution of a previous episode of diarrhea episode and cessation of treatment comprising a 10-day period. Data suggest that the rate of CDAD recurrence is between 10% and 25% at a cost of between $3.2 and $4.8 billion, Dr. Nijim said. Glucocorticoids are known risk factors for acquiring CDAD, likely due to their immunosuppressive effects, and PPIs have also been suggested as risk factors for acquiring CDAD, although the findings have been mixed. Likewise, treatment with metronidazole for an initial episode has been linked with treatment failure and recurrence risk. In the current study, one of the largest to date to evaluate factors associated with CDAD recurrence, both PPIs and glucocorticoids were shown to be associated with recurrence risk, but no link was found between metronidazole or any CDAD treatment modality and recurrence, Dr. Nijim said. Though limited by the single-center, retrospective study design and its inherent information and selection biases, the study includes a large ICU patient sample, and the findings suggest that intensivists should watch carefully for recurrence in patients using PPIs and/or steroids. Also, clinicians should think carefully before starting patients on PPIs – and perhaps use histamine blockers instead – in patients with a history of CDAD, she said.

Topical steroid might improve mucosal integrity in eosinophilic esophagitis

FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Topical steroid therapy improved some indicators of mucosal integrity in patients with eosinophilic esophagitis, but proton pump inhibitor therapy did not, according to two studies reported in the November issue of Clinical Gastroenterology and Hepatology. The first study found that topical fluticasone therapy at a dose of 880 mcg twice daily for 2 months helped correct esophageal spongiosis, or dilated intercellular space, in patients with eosinophilic esophagitis (EoE). Spongiosis scores for treated patients were significantly lower than for untreated patients (0.4 vs. 1.3; P = .016), said Dr. David Katzka at the Mayo Clinic in Rochester, Minn. and his associates (Clin. Gastroenterol. Hepatol. 2014 [doi:10.1016/j.cgh.2014.02.039]). In the study, histologic analyses also showed that improved spongiosis scores in treated patients correlated with increased density of two tight junction proteins, filaggrin (P = .001) and zonula occludens-3 (P = .016), said the investigators. These proteins might help regulate antigenic penetration of the esophageal mucosa and also could permit migration of white blood cells, they said. “Loss of tight junction regulators and dilation of intercellular spaces appear to be involved in the pathophysiology of EoE and could be targets for treatment,” the researchers concluded. But they also noted that their study did not examine the same patients before and after steroid therapy and did not look at desmosomes, intercellular junctions that past research has suggested might be affected in EoE. For the second study, Dr. Bram van Rhijn and his associates at the Academic Medical Center in the Netherlands compared endoscopies of 16 patients with dysphagia and suspected (unconfirmed) EoE with 11 controls, both at baseline and after 8 weeks of high-dose esomeprazole treatment. Esophageal mucosal integrity was “severely impaired” in patients with confirmed EoE and in those with proton pump inhibitor–responsive eosinophilia (PPRE), the researchers said (Clin. Gasteroenterol. Hepatol. 2014 [doi:10.1016/j.cgh.2014.02.037]). In both forms of disease, molecules as large as 40,000 daltons were able to pass through the compromised esophageal mucosa, Dr. Bram van Rhijn and his associates reported. “This size is similar to the size of most plant and animal food allergens to which EoE patients are sensitized,” they added. Esophageal permeability might increase the rate of immune exposure to allergens, thereby mediating EoE and PPRE, they said. On mucosal functional tests, both EoE and PPRE were associated with reduced transepithelial electrical resistance and lower electrical tissue impedance, most notably in patients with EoE (P less than .001 for both, compared with controls), the investigators reported. Proton pump inhibitor treatment partially reversed these changes in patients with PPRE but showed no effect for patients with EoE, they said. This finding suggests that acid reflux might play a role in PPRE, but not in EOE, they concluded.

Adjustable Intragastric Balloons: A 12 Month Pilot Trial in Endoscopic Weight Loss Management

Objectives Intragastric balloons(IGBs) are associated with, 1) intolerances in the early period, 2) diminished weight loss after the third month, 3) risk of bowel obstruction mandating removal at six months, and 4) the need for a dedicated extraction tool.The introduction of an adjustable balloon could improve comfort and offer greater efficacy. A migration prevention function, safely enabling prolonged implantation, could improve efficacy and weight maintenance post extraction. Polypectomy snare extraction would also be beneficial. The first implantations of an adjustable balloon with attached migration-prevention anchor is reported.

Aims & Methods The SpatzTM Adjustable Balloon is mounted on a curled non-crushable catheter that straightens overa guidewire, and passed transorally, under conscious sedation. The non-crushability of the catheter loops is mediated by an internal chain. Post-implantation, an extractable inflation tube housed in the catheter can be snared endoscopically and pulled outside the mouth for volume adjustments. 18 patients (15 female, 3 male); mean BMI 39,4(range 29,4 to 53,2); and mean wt. 114,9kg (range 73,5 to 163kg) were implanted with mean balloon volume of 406,9 cc (range 350 to 600cc) of saline.

Results Mean weight loss at 24 weeks was 15.6 kg with a 26.4% EWL (% excess weight loss), and 35.5 kg with a 67.3 %EWL at 52 weeks. Sixteen adjustments were successfully performed. Six downward adjustments alleviated intolerance, yielding an additional mean weight loss of 4.6 kg. Ten upward adjustments for weight loss plateau yielded a mean additional weight loss of 8.1 kg. There were no major complications, however, seven of the 18 balloons were removed.

Conclusion The Spatz ABS has been successfully implanted in eighteen patients. 1) Upward adjustments yielded additional weight loss. 2) Downward adjustments alleviated intolerance, with continued weight loss. 3) Eight extractions were performed with a polypectomy snare. 4) Preliminary one year results are encouraging.



Jeffrey Brooks et al

Symptomatic bacterial contamination of an intragastric balloon

A 45-year-old woman had an intragastric balloon placed endoscopically for metabolic syndrome and obesity (body mass index = 37.42 kg/m2). She was being maintained on omeprazole daily. Under endoscopic view, the balloon was positioned in the stomach and inflated with 650 mL of 0.9% NaCl mixed with 20 mL of methylene blue solution. After 4 months, the patient had lost 22 kg but began to report intense nausea, vomiting, abdominal distention, and abdominal pain. An abdominal plain film showed a radiolucent and elongated structure in the upper abdomen (A). Endoscopy revealed an enlarged balloon, and the solution inside the balloon was collected during its removal by puncture. Inspection of the balloon after withdrawal showed its surface to be irregular with microbubbles and what appeared to be extensive fungal colonization (B). No samples were taken from the balloon surface, but culture and examination of the solution inside the balloon revealed Klebsiella pneumoniae (a gas-producing bacterium) and Candida spp. The patient was discharged without any symptoms and remained asymptomatic during the next 3 months. Disclosure All authors disclosed no financial relationships relevant to this publication. Commentary Patients with intragastric bezoars lose weight, an observation that prompted Mary and Lloyd Garren to develop the first intragastric balloon to function as an artificial bezoar, ostensibly by inducing a feeling of satiety and thereby helping to curb appetite. In 1985, the U.S. Food and Drug Administration approved the use of a 200-mL air-filled cylindrical, but sharp-edged, plastic bubble, ie, the Garren-Edwards Gastric Bubble, for use in morbidly obese patients, as an adjunct to dietary and behavior modification therapy. Other intragastric balloons have been developed and tried since then and have indeed resulted in weight loss, which sometimes was quite significant, although several randomized, controlled studies failed to show a significant advantage of the balloon over a sham procedure. Reported complications of intragastric balloons have included gastric ulceration, bubble intolerance, and, perhaps most important, spontaneous deflation of the bubble with resultant intestinal obstruction, the risk of which is significantly higher when balloons are left in place longer than 6 months. Here the authors report another adverse effect, namely, abdominal distention and pain, attributed to gas production by Klebsiella. The observation of Klebsiella in the balloon raises many questions: Why was the inner balloon not sterile? What happened to balloon permeability over the time that the balloon resided in the stomach? Was inner colonization a local phenomenon facilitated by the clumps of microorgansims on the external surface of the balloon? One would imagine that were gastric acid to have been normal, there probably would not have been a proliferation of “fungal-appearing” forms nor of bacteria other than Helicobacter pylori. How does the presence of an intragastric balloon affect gastric acid secretion? So many questions. Winnie the Pooh said, “No one can be uncheered with a balloon.” Although this balloon probably led to some cheering at first, it then, I am sure, lead to uncheering as reality set in: obesity is a major health problem that involves lifelong attention to diet, behavior modification, and perhaps the help of a skilled surgeon. I wish this patient good fortune.

Study finds no link between TNF-alpha blockers, cancer in inflammatory bowel disease

A large registry-based study has found no increased risk of cancer in inflammatory bowel disease patients treated with tumor necrosis factor alpha (TNF-alpha) antagonists. The findings, from the Danish National Patient Registry, are based on 56,146 inflammatory bowel disease (IBD) patients. "Given the upper limit of the conference intervals, this study could rule out a more than 36% relative increase in the risk of overall cancer over a median follow-up of 3.7 years among TNF-alpha antagonist-exposed patients, with 25% of these followed for 6 years or longer," Dr. Nynne Nyboe Andersen of Herlev University Hospital in Copenhagen told Reuters Health in an email. The findings are published in the June 18 issue of JAMA. Concerns had been raised that TNF-alpha antagonists might increase cancer risk through their immunosuppressive effects, Dr. Andersen and colleagues note in their report. Three studies of the issue have been done in IBD patients, with negative findings, but very short follow-up periods. In the current study, the researchers looked at IBD patients ages 15 years and older, including 4553 (8.1%) who had been treated with TNF-alpha antagonists. Their analysis included 489,433 person-years of follow-up, during which time 81 patients (1.8%) exposed to TNF-alpha antagonists developed cancer, and 3465 patients (6.7%) not exposed to the drugs were diagnosed with cancer. After Poisson regression analysis adjusting for age, calendar year, disease duration, propensity scores, and other IBD medication use, the relative risk associated with TNF-alpha antagonist use was 1.07, and not significant. The researchers also performed stratified analyses based on cumulative TNF-alpha antagonist dose and time since first TNF-alpha antagonist dose, but found no association with cancer risk. Their analysis also did not find an increased risk by cancer type. "Keeping in mind the often protracted progression of cancer, there is a need for future studies with an even longer follow-up time to evaluate the risk of cancer in patients exposed to TNF-alpha antagonists," Dr. Andersen said. "Further, it should be noted that due to the relatively small sample size and the small number of cancer cases in our study, statistical power was limited in subgroup analyses of site-specific cancer and there is a need for larger future studies to assess the risk in different types of cancer." Dr. William Sandborn, director of the IBD Center at the University of California, San Diego, reviewed the study for Reuters Health. He noted that the issue of TNF-alpha and cancer risk in IBD has not been a major concern. However, he added, the IBD drugs azathioprine and 6-mercaptopurine have clearly been linked to cancer. "They are unequivocally linked with a higher risk of non-melanoma skin cancer and a higher risk of non-Hodgkin lymphoma," Dr. Sandborn said. Studies have shown that combination therapy with azathioprine and TNF-alpha antagonists is more effective than either drug given as monotherapy, he added. The question that needs to be answered, he said, is how the benefit of combination therapy compares to the increased cancer risk seen with azathioprine. "I hope the authors will continue to mine their data to further explore the relationship of the whole range of drugs we use in IBD and cancer," he said.

Monitor elderly for bone loss after gastric bypass

CHICAGO (FRONTLINE MEDICAL NEWS) – Older adults who undergo Roux-en-Y gastric bypass are at risk for lessened bone mineral density for at least 2 years after their surgery and should be monitored appropriately for osteoporosis or fragility fractures, according to investigators from Massachusetts General Hospital in Boston. Two years postoperatively, vertebral bone mineral density (BMD) in 30 patients was about 7% lower on quantitative computed tomography (QCT) and 6% lower on dual-energy x-ray absorptiometry (DXA) – both methods were used to ensure accuracy – when compared with 20 well-matched, morbidly obese controls. Total hip BMD was 6% lower on QCT and 10% lower on DXA. Femoral neck BMD was about 6% lower by both measures. Biomarkers of bone turnover remained markedly elevated in surgery patients, as well, but unchanged in controls (C-telopeptide 0.65 ng/mL vs. 0.3 ng/mL; amino-terminal propeptide of type I collagen 65 ng/mL vs. 40 ng/mL). The findings were all statistically significant. The groups started to separate early on BMD, and there’s concern that bone loss will continue for more than 2 years after surgery. Preoperatively, most Roux-en-Y gastric bypass patients have a higher than normal BMD, “so even a loss of 10% over 2 years is not going to put most of them in the osteopenic or osteoporotic range. The caveat now is that we are [offering surgery] to older patients and adolescents. Elderly patients are starting with lower bone mass, so there are concerns about [post-op] skeletal fragility. The oldest patient in our study was 72. She became osteoporotic after surgery because her bone density was low to begin with,” said lead investigator Dr. Elaine W. Yu, an endocrinologist at Massachusetts General. “In adolescents, there are implications for achieving peak bone mass. Even if you have a normal bone density 2 years after surgery, what’s going to happen in 10 years, 20 years?” she asked. In short, “people should pay attention to bone density and bone loss and discuss this as one of the potential negative effects of bariatric surgery. For patients at risk, you should definitely consider serial bone density monitoring and osteoporosis therapy if needed,” she said at the joint meeting of the International Society of Endocrinology and the Endocrine Society. At baseline, both subjects and controls were about 47 years old and 270 pounds, with a mean a mean body mass index of 45 kg/m2. About 85% were women. The study excluded patients with histories of bone disorders or use of bone-affecting medications. Surgery patients lost a mean of about 85 pounds in the first 6 months; their weight loss then stabilized, but they continued to lose bone. Controls stayed about the same weight. The findings can’t be explained by post-op calcium or vitamin D depletion. “These subjects were aggressively supplemented with both,” and both groups maintained normal levels throughout the study. Also, there were no statistical differences in parathyroid hormone levels between the groups. “Our theory is that there are changes in gut hormones after gastric bypass that have direct effects on bone, like ghrelin,” Dr. Yu said. The National Institutes of Health funded the work. Dr. Yu is a consultant for Amgen.