A SVR24 (undetectable levels of HCV RNA in serum 24 weeks after completion of therapy) is considered to indicate successful treatment—most patients who achieve SVR24 maintain their serum-negative status and have reduced complications from liver disease and increased survival times. It is therefore the primary endpoint of HCV therapy trials for regulatory approval—efficacies of all HCV therapies approved by the US Food and Drug Administration have been based on the proportion of patients attaining SVR24. However, earlier time points could increase efficiency of drug development.

Jianmeng Chen et al. assessed data from 15 phase 2 and 3 trials, 3 pediatric studies, and 5 drug-development programs to determine the concordance between SVR24 and SVR12, and even SVR4. They analyzed data from groups of subjects who received various combinations and regimens with interferon, ribavirin, and direct-acting antiviral agents.

Of the 13,599 adult subjects in the database analyzed, 50.6% achieved SVR24 and 51.8% achieved SVR12. These appeared to be mostly the same patients—the positive predictive value of SVR12 for SVR24 was 98% and the negative predictive value was 99% among subjects with genotype 1 HCV infection. A similar level of concordance was observed in subjects with HCV genotype 2 or 3 infections, as well as in pediatric studies.

The positive predictive value of SVR4 for SVR24 was 91% and the negative predictive value was 98% in subjects with genotype 1 HCV infection. Chen et al. observed similar values regardless of subjects’ race, sex, treatment experience, genotype 1a vs 1b, or presence of cirrhosis.

Why is there such a high level of agreement between SVR12 and SVR24, and to a lesser extent SVR4 and SVR24? Chen et al. explained that 65% of subjects who relapsed had detectable viral load by week 4 after treatment and 95% had detectable viral load by week 12. So if the virus is going to reappear, in generally does so within 12 weeks after the treatment ends.

The authors conclude that individual patients should be followed for 24 weeks or longer after treatment to confirm their responses. But SVR12, which is currently used as supportive information for registration trial design, can also be appropriate for regulatory approval of treatment regimens.

More Information on HCV Infection

• The CDC Website on Hepatitis C
• The US National Library of Medicine Website on HCV
• The World Health Organization Website on HCV

Read the article online.
Chen J, Florian J, Carter W, et al. Earlier sustained virologic response end points for regulatory approval and dose selection of hepatitis c therapies. Gastroenterology 2013;144:1450–1455.e2.

One way to reduce pancreatic cancer mortality could be to identify tumor precursors, while they are still treatable. The most common precursors to pancreatic adenocarcinoma are microscopic, pancreatic intraepithelial neoplasias (PanINs) and larger cystic precursor neoplasms called intraductal papillary mucinous neoplasm (IPMNs). These are generally asymptomatic and are identified only incidentally or by screening.

Markers are needed to accurately distinguish early invasive pancreatic cancers and high-grade dysplasia (PanIN-3 and IPMNs with high-grade dysplasia) from lesions with low-grade dysplasia, so physicians can determine management and surveillance strategies. The tumor protein 53 (TP53) gene is mutated in approximately 75% of invasive pancreatic cancers, with a similar prevalence in familial and sporadic pancreatic cancers.

Mitsuro Kanda et al. therefore looked for TP53 mutations in pancreatic juice samples from 180 participants in the US multicenter Cancer of the Pancreas Screening (CAPS) trials, comparing their findings with the eventual diagnosis, based on surgery or fine-needle aspiration.

They found that detection of TP53 mutations in duodenal samples of pancreatic juice identified 67.4% of patients with pancreatic ductal adenocarcinomas and 50% with high-grade lesions (PanIN-3 and high-grade IPMN). TP53 mutations were not identified in duodenal samples from 58 controls or 55 individuals without evidence of advanced lesions (see figure).

Prevalence of TP53 mutation by diagnostic group.

Kanda et al. also analyzed frozen section samples from a different set of patients, and found TP53 mutations in 9.1% of intermediate-grade IPMNs, 17.8% of intermediate-grade PanINs (PanIN-2), 38.1% of high-grade IPMNs, 47.6% of PanIN-3, and 75% of 20 invasive ductal adenocarcinomas (one cancer had 2 mutations). No TP53 mutations were detected in low-grade PanINs (PanIN-1) or IPMNs.

One participant of the trial did not have any evidence for a mass based on imaging analyses, but a duodenal sample of pancreatic juice was found to have a TP53 mutation. Thirteen months after the initial screening examination, this patient was found to have a pancreatic ductal adenocarcinoma that contained the same TP53 mutation, indicating the limitations of current imaging tests in screening for pancreatic cancer.

In an editorial that accompanies the article, Manoop S. Bhutani et al. state that the study shows a promising role for TP53 mutation analysis in identifying patients with pancreatic cancer and earlier lesions. However, because of the overall low sensitivity of the analysis, it can’t be used alone for screening purposes—it is most likely to be used in conjunction with imaging techniques such as endoscopic ultrasound and magnetic resonance imaging.

Bhutani et al. add that in addition to screening duodenal samples of pancreatic juice for TP53 mutations, analyses of other biomarkers (mutations in DNA, secreted proteins and glycoproteins, and microRNAs), and incorporation of other technologies might increase our ability to identify patients at highest risk for pancreatic cancer.

More information on Pancreatic Cancer

• NCI Website on Pancreatic Cancer
• The CAPS Trial

Read the article online. Kanada M, Sadakari Y, Borges M, et al. Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia. Clin Gastroenterol Hepatol 2013;11:719-730.e5

Read the accompanying editorial. Bhutani M, Thosani N, Suzuki R, et al. Pancreatic cancer screening: what we do and do not know. Clin Gastroenterol Hepatol 2013;11:731–733

Many medications, such chlorpromazine, azathioprine, and sulfasalazine, can cause liver injury, but it is not clear what proportion of patients develop liver disorders because it is not known exactly how many patients take potentially hepatotoxic drugs.

Einar Björnsson et al. assessed the incidence, severity, and outcomes of patients with DILI using the well-characterized population of Iceland (about 250,000 adults, similar to the population of Orlando, Florida) and its centralized medical care system. “Very few well-designed studies of incidence have been undertaken,” he explained in a video abstract of the article.

Video abstract from Einar Björnsson

Björnsson et al. systematically collected information on all cases of acute DILI that occurred in Iceland from outpatient prescription drugs. The also examined the Icelandic Medicines Registry records of prescriptions for all drugs associated with DILI that had at least a possible causal relationship. Liver injury was defined by levels of alanine aminotransferase more than 3-fold the upper limit of normal and/or alkaline phosphatase levels more than 2-fold the upper limit of normal. Their analysis did not include patients with acetaminophen toxicity.

They identified 96 cases of DILI over the 2 year period. Because they knew the population from which these cases arose, they were able to estimate the incidence of drug-induced liver disease—they calculated this to be 19 cases per 100,000 persons/y, which is higher than previous estimates.

Surprisingly, only 27% of patients had jaundice; rash occurred in 10%, fever in 6%, and many of the patients complained of asthenia and itching. Several other important findings were that the incidence of DILI was similar in women and men, but increased with age (from 9/100,000 among 15- to 29-year-olds to 41/100,000 among patients). The increase in rates with age paralleled the increase use of medications—the elderly were more likely to develop liver injury from medications because they are more likely to take them.

The crude annual incidence rate of DILI was 19.1 cases per 100,000 inhabitants. DILI was caused by a single prescription medication in 75% of cases, by dietary supplements in 16%, and by multiple agents in 9%.

The most commonly implicated drugs were amoxicillin-clavulanate (22%), diclofenac (6%), azathioprine (4%), infliximab (4%), and nitrofurantoin (4%). The median duration of therapy was 20 days, and 22 patients were hospitalized (23%) for a median of 5 days. “The highest risk of hepatotoxicity in our study was associated with use of azathioprine and infliximab,” Björnsson says in the video abstract.

In an editorial that accompanies the article, Jay Hoofnagle and Victor Navarro say that DILI is not a single disease of the general population, but rather a series of rare diseases that occur only in persons who take specific medications.

Read the article online. This article has an accompanying continuing medical education activity.
Björnsson ES, Bergmann OM, Björnsson HK, et al. Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology 2013;144:1419-1425.e3.

Read the accompanying editorial.
Hoofnagle JH, Navarro VJ. Drug-induced liver injury: Icelandic lessons. Gastroenterology 2013;144:1335-1336.

Celiac disease is caused by an immune response to ingested gluten—a protein found in wheat, barley, rye, and possibly oats.

Over time, this reaction produces inflammation that damages the lining of the small intestine and prevents absorption of some nutrients. As many as 70% of untreated patients with celiac disease have reduced bone mineral density, which increases risk for osteoporosis and overall fractures by 30%.

Symptomatic individuals and those in high risk groups (who have family members with the disease) are typically screened for celiac disease by serologic tests, followed by endoscopy. Although these tests are relatively inexpensive and detect celiac disease with high levels of sensitivity and specificity, it is not clear if all people should be screened (i.e., universal screening), partially because of unclear long-term benefits to patients—especially if they are asymptomatic.

K.T. Park et al. constructed a decision analytic Markov model to compare the predicted cost-effectiveness of universal serologic screening of adolescents (12 years old) with that of standard screening (of only symptomatic adolecents or those with genetic risk factors for celiac disease), based on their ability to prevent hip and vertebral fractures.

They found that compared with the standard screening strategy, universal screening was not only more costly, but had a lower effect on quality of life for each sex, based on its ability to prevent bone loss and fractures among patients with undiagnosed or subclinical disease.

Park et al. conclude that adopting the universal screening strategy, in which virtually every preadolescent child would be routine screened for CD in the primary care setting, would be more expensive and fail to increase the long-term quality of life for entire population. They add that it could result in unnecessary endoscopic evaluations of healthy individuals when serologic tests produce false-positive results.

The authors recognized the concern that standard practice of screening for celiac disease misses a considerable proportion of asymptomatic CD patients. However, they say that there is no formal consensus on the precise long-term health benefits, if expanded screening effectively decreases the proportion of undiagnosed or untreated CD patients.

More Information on Celiac Disease:

• Mayo Clinic website on celiac disease
• NIDDK website on celiac disease

Read the article online.
Park KT, Tsai R, Wang L, et al. Cost-effectiveness of universal serologic screening to prevent nontraumatic hip and vertebral fractures in patients with celiac disease. Clin Gastroenterol Hepatol 2013;11:645–653.

Pancreatology is a rapidly developing field—recent findings from molecular and genetic studies are being developed into new treatment strategies. To update readers on the latest findings, as well as provide them with a historical perspective of the field, Gastroenterology presents The Pancreas: Biology, Diseases, and Therapy. The issue contains 17 review and commentary articles written by leading experts in pancretology research, covering everything from the basic biology of the pancreas to pancreatic disorders and therapeutic strategies.

Editors Diane Simeone and Stephen Pandol say that they hope this resource will “inspire our readers not only by knowledge transfer but also in ways that will lead to new discoveries and therapies to improve the lives of patients afflicted with pancreatic disorders”.

Review the full table of contents for the special issue.
The pancreas: biology, diseases and therapy. Gastroenterology 2013;144:1163-1326.

PSC is a chronic, cholestatic liver disease that eventually leads to cirrhosis and liver failure, requiring transplantation. Little is known about the pathogenesis of PSC, but 70%–80% of patients also have IBD, so immune dysregulation and loss of tolerance to gut bacteria could be involved.

PSC-associated IBD is phenotypically different from IBD in patients without liver disease, with an increased frequency of pancolitis, rectal sparing, and backwash ileitis, and a milder clinical course of colitis. Patients with PSC-associated IBD have a greater risk for colorectal neoplasia than patients with only IBD, and their risk increases even further after liver transplantation.

Kristin Kaasen Jørgensen et al. investigated whether differences in IBD activity after liver transplantation were affected by immunosuppressive regimens or other factors related to the transplantation. They used a Nordic liver transplant registry to follow 439 patients with PSC who underwent liver transplantation (353 had IBD at the time of transplantation), and compared patients’ course of IBD before and after liver transplant.

They found that IBD activity either decreased or remained unchanged in 60% of patients after liver transplantation, but worsened in 40% of patients. Patients with worsened disease had increased levels of colon inflammation, number of relapses, overall IBD activity, and risk of colectomy.

Dual immunosuppressive therapy with tacrolimus and mycophenolate mofetil (MMF) was associated with increased IBD activity after transplant, whereas the combination of cyclosporine A and azathioprine appeared to protect against IBD.

Ten of 11 patients who developed de novo IBD had received tacrolimus after liver transplantation. The authors were surprised to find this association, because tacrolimus is a well-established treatment for IBD.

In an editorial that accompanies the article, Udayakumar Navaneethan and Bret A. Lashner propose that tacrolimus could increase intestinal permeability and endotoxemia to induce an inflammatory response. Alternatively, tacrolimus might reduce T-cell apoptosis to a greater extent than cyclosporine to promote colon inflammation.

Jørgensen et al. say that it is difficult to determine whether the association with deteriorated IBD activity after liver transplantation was caused by tacrolimus, MMF, or by synergistic effects of the combination therapy.

Nonetheless, Navaneethan and Lashner conclude that patients with PSC-IBD need careful and regular follow-up evaluation and monitoring for IBD after liver transplantation—every subsequent visit should include questions about bowel symptoms. Patients also require yearly follow-up surveillance colonoscopy for colon neoplasia—even in patients with no disease activity.

Navaneethan and Lashner state that physicians should consider the use of a tacrolimus-free immunosuppressive regimens for patients with IBD at the time of liver transplantation. Further studies are needed to determine whether cyclosporine or sirolimus with MMF could be used safely without affecting graft rejection and exacerbating IBD activity.

More Information on PSC

• The NIDDK Website on PSC

Read the article online.
Jørgensen KK, Lindström L, Cvancarova M, et al. Immunosuppression after liver transplantation for primary sclerosing cholangitis influences activity of inflammatory bowel disease. Clin Gastroenterol Hepatol 2013;11:517–523.

Read the accompanying editorial.
Navaneethan U, Lashner BA. Effects of immunosuppression and liver transplantation on inflammatory bowel disease in patients with primary sclerosing cholangitis. Clin Gastroenterol Hepatol 2013;11:524-525.

Biliary atresia is a progressive fibro-inflammatory disorder of infants that involves the extrahepatic and intrahepatic biliary tree and causes obliteration of the ducts, leading to cholestasis, fibrosis, and cirrhosis. If uncorrected, it causes death within the first 2 years of life.

The causes of this disease are unknown, but are believed to involve exposure of a genetically susceptible individual to specific environmental factors.

Biliary atresia occurs exclusively in neonates, so variants of genes expressed during hepatobiliary development could affect susceptibility. Genome-wide association studies previously identified a region of interest at 2q37.

Shuang Cui et al. took a closer look at the chromosome region, searching for copy number variants that were increased among 61 children with the disease, compared with 5088 healthy individuals.

They found that the patients had a significant increase in deletions at 2q37.3 that resulted in deletion of one copy of GPC1. This gene encodes glypican 1—a heparan sulfate proteoglycan that regulates hepatogenesis, Hedgehog signaling, and inflammation.

To learn how deletion of GPC1 could affect biliary development, they reduced its expression in zebrafish. Zebrafish are useful for studying development—embryos develop rapidly ex utero, and their hepatobiliary development and anatomy are similar to those of mammals. By 5 days after fertilization, the zebrafish liver has distinct hepatocytes and cholangiocytes, with an interconnecting duct network. Organs in embryonic zebrafish can be imaged in vivo, and gene expression can be reduced using morpholino antisense oligonucleotide-mediated knockdown techniques.

Cui et al. found that knockdown of gpc1 in developing zebrafish led to intrahepatic biliary and gallbladder defects, observed at the late larval stage (5 days after fertilization). During normal embryogenesis, zebrafish at this stage have developed intrahepatic main ducts, interconnecting branches, and terminal ductules. The knockdown fish had fewer cholangiocytes, resulting in a less complex architecture than controls (see below figure).

Gpc1 knockdown zebrafish (gpc MO) have a decreased number and complexity of ducts, compared with controls. Cells are indicated by white dots.

Bile secretion was also significantly reduced in gpc1 knockdown fish.

Activity of the signaling protein Hedgehog is increased in patients with biliary atresia, and GPCs are known to regulate its activity. Cui et al. compared expression of genes known to be regulated by Hedgehog (gli2a, ptch1, floxl1, znf697, and ccnd1), and found it to be increased in livers from gpc1 knockout embryos.

Exposure of the gpc1 knockout fish to cyclopamine, a Hedgehog antagonist, partially reversed the biliary defects. On the other hand, injection a Hedgehog ligand led to biliary defects similar to those of the gpc1 knockdowns.

The authors propose that these findings are consistent with a model in which glypicans modulate Hedgehog activity by acting as a sink, decreasing the availability of ligand—the absence of glypican increases Hedgehog signaling.

Cui also found that liver samples from patients with BA had reduced levels of apical GPC1 in cholangiocytes, compared with samples from controls.

This is the first study to identify a potential risk gene in patients with biliary atresia and to show functional defects in the biliary system in a model organism. These findings also support a role for Hedgehog signaling in the pathogenesis of BA.

In an editorial that accompanies the article, Alexander Miethke and Stacey Huppert state that Cui et al. have shown that zebrafish are a useful tool to assign biological significance to results of genomic studies.

More Information on Biliary Atresia

• NIDDK Website on Biliary Atresia

Read the article online.
Cui S, Leyva–Vega M, Tsai EA, et al. Evidence from human and zebrafish that gpc1 is a biliary atresia susceptibility gene. Gastroenterology 2013;144:1107−1115.e3.

Read the accompanying editorial.
Miethke AG, Huppert SS. Fishing for biliary atresia susceptibility genes. Gastroenterology 2013;144:878−881.

Patients with risk factors for GI disorders who continuously take NSAIDs (such as diclofenac, ketoprofen, piroxicam, and naproxen) should also take gastroprotective agents, such as a proton pump inhibitor (PPI), according to current guidelines.

However, it is not clear how many physicians continue to prescribe gastroprotective drugs to their patients, or whether stopping the prescription increases GI complications.

Isabelle Le Ray et al. assessed prescription data from 1856 patients in France who were at risk for GI events and had received prescriptions for an NSAID and PPI, from 2007 to 2009.

They found that about 78% of patients were still being prescribed a PPI along with an NSAID after 1 year, but only about 68% were still being co-prescribed the PPI after 2 years (see below figure).

Decrease in co-prescription of PPIs with NSAIDs over time.

The risk for upper GI injury (gastralgia, gastritis, ulcer) increased by almost 50% among patients that stopped receiving the PPI co-prescription. This finding was consistent with a recent study reporting higher rates of GI adverse events and shorter NSAID treatment among patients who were noncompliant with their PPI therapy.

The patients most likely to no longer receive a prescription for a PPI were those who had switched to a cyclooxygenase (COX)-2–selective inhibitor or nonselective NSAID. This is a concern, because international guidelines recommend co-prescription of a PPI with a COX-2 inhibitor for patients at high risk for GI complications. Women were also more likely to stop receiving a PPI prescription.

Half that patients that stopped receiving a prescription for PPI received it again within 6 months, indicating that the change was unintentional. It could be that these patients reported dyspepsia or another symptoms, such as gastroesophageal reflux, to their doctors.

In an editorial that accompanies the article, Angel Lanas says that failure to renew prescriptions for gastroprotective agents is an important factor to consider in planning strategies to reduce the GI damage induced by NSAIDs.

Le Ray et al. conclude that the increased frequency of GI adverse events among patients without appropriate PPI coverage indicates the need to optimize the PPI prescription procedure. One way that under-prescription might be avoided would be to create a combination pill, which contains an NSAID and a PPI.

Read the article online.
Le Ray I, Barkun AN, Vauzelle–Kervroëdan F, et al. Failure to renew prescriptions for gastroprotective agents to patients on continuous nonsteroidal anti-inflammatory drugs increases rate of upper gastrointestinal injury. Clin Gastroenterol Hepatol 2013;11:499–504.e1.

Read the accompanying editorial.
Lanas A. Compliance with prescriptions of appropriate therapy for NSAID users: is the glass half empty or half full? Clin Gastroenterol Hepatol 2013;11:505–506.

Stem cells have been reported to exist in the basal layer of the human esophagus—their progeny are believed to become differentiated in the parabasal and superficial layers. These cells might be isolated and studied to develop new therapies for disorders such as Barrett’s esophagus—a premalignant condition in which the stratified squamous epithelium is replaced by a columnar metaplasia.

However, studies of stem cells in the gastrointestinal tract have been limited by the constraints of experimental systems—it is not clear which models are most relevant to the human gastrointestinal tract, or how they differ among benign, premalignant, and neoplastic tissues.

Qiuwei Pan et al. investigated the existence of uncommitted, slowly cycling cells in esophageal and stomach tissues of patients, tracking cells labeled by 5-iodo-2′-deoxyuridine (IdU). Cells that retain this label for more than 29 days, called label-retaining cells, are believed to be a population of adult stem cells—long-lived, multi-potent cells responsible for the replacement of differentiated cells after injury or insult.

The authors injected IdU into 4 patients undergoing esophageal resection for adenocarcinoma. Tissues were collected 7, 11, 29, and 67 days later, from areas of squamous esophagus, Barrett’s esophagus, Barrett’s-associated dysplasia, esophageal adenocarcinoma, and normal stomach.

Pan et al. found label-retaining cells in the human esophagus and stomach that had many features of stem cells (long lived, slow cycling, uncommitted, and multi-potent).

In normal squamous esophagus, label-retaining cells were detected mainly in the basal layer, which became the exclusive location by 67 days (see below figure).

The normal squamous esophageal epithelium. The interpapillary basal layer is red, the papillary basal layer is green, the parabasal layer is orange, and the superficial layer is brown.

These cells were epithelial (in that they contained cytokeratin) and resided adjacent to clusters of proliferating cells. The authors also calculated the epithelial turnover time of the healthy esophageal mucosa to be approximately 11 days (twice that of the intestine).

In normal stomach, Pan et al. identified LRCs in only the neck of the gastric unit; these cells were also epithelial yet undifferentiated (see below figure).

Label-retaining cells (red) in the stomach co-localize with cytokeratin (green) at 11 days post-infusion, confirming the epithelial nature of these cells.

Barrett’s esophagus forms glandular structures; cells proliferate in the base and further up in the glands and become differentiated toward the surface before being lost in the lumen.

In patients, Pan et al. found label-retaining cells only at the base of the Barrett’s glands, through 67 days after infusion of the label. These cells were epithelial and located near proliferating cells, and did not appear to be committed to any particular lineage. LGR5 mRNA, a previously identified marker of intestinal stem cells, was also found at the base of the Barrett’s glands.

Pan et al. conclude that they have demonstrated the existence of a population of slowly cycling, uncommitted cells in the normal and metaplastic human upper gastrointestinal tract. Further studies of these could lead to new approaches for regenerative medicine, and aid diagnosis and determination of prognosis for patients with Barrett’s esophagus.

Read the article online.
Pan Q, Nicholson AM, Barr H, et al. Identification of lineage-uncommitted, long-lived, label-retaining cells in healthy human esophagus and stomach, and in metaplastic esophagus. Gastroenterology 2013;144:761–770.

Bariatric surgeries include Roux-en-Y gastric bypass (RYGB), laparoscopic adjustable gastric band (LAGB), vertical banded gastroplasty (VBG), sleeve gastrectomy (SG), biliopancreatic diversion, and duodenal switch procedures. RYGB is performed more frequently and leads to an average percent excess weight loss of 56.7%–66.5% in the first 24 months after surgery. Diabetes resolves or improves in 86% of patients, hypertension in 68%, obstructive sleep apnea in 81%, and hyperlipidemia in 97%.

The digestive pathway following RYGB.

However, bariatric surgery can cause complications such as nausea, vomiting, and abdominal pain. According to Nitin Kumar and Christopher Thompson, to help patients with these side effects, gastroenterologists must be aware of which surgery the patient received and when it was performed, whether subsequent revisions were performed, and whether certain habits or risk factors could cause the complications. Endoscopic procedures are frequently required to evaluate and treat patients with these complications.

For example, gastrointestinal bleeding occurs more commonly after RYGB (1.9% of cases) than LAGB, SG, or VBG. Bleeding can develop at multiple sites, including the pouch, anastomoses, staple lines, the contiguous small intestine, the excluded stomach, or the bypassed small intestine. Kumar and Thompson explain that if endoscopy is performed, air insufflation should be minimized, and carbon dioxide insufflation should be used. Endoclips can be used to stop the bleeding, in conjunction with epinephrine injection. Electrocautery should be avoided at fresh staple lines.

About 20% of patients who undergo RYGB develop ulcers at the gastrojejunal anastomosis—most frequently in the first 3 months after surgery, but ulcers can develop at any time. Signs of ulcers include epigastric pain, nausea, vomiting, food intolerance, and bleeding.

Kumar and Thompson say that following bariatric surgery, endoscopy can be safely performed to investigate the gastric pouch, gastrojejunal anastomosis, and proximal Roux limb. For patients who have undergone RYGB, anastomotic ulcers should be treated with soluble proton pump inhibitors. Bile reflux can be treated with bile acid binders such as cholestyramine or colestipol. Patients should stop taking non-steroidal anti-inflammatory drugs, if possible, or combine them with proton pump inhibitors.

Endoscopy can be used to identify and treat other complications, such as removing foreign materials and repairing stenosis, leaks, and fistulas. Pancreatic and biliary disorder can be treated with endoscopic ultrasound and endoscopic retrograde cholangiopancreatography.

One of the biggest complications after bariatric surgery is weight regain—approximately 20% of patients have not lost 50% of their excess weight within 1 year of surgery. Furthermore, 30% of patients gain the weight back by 2 years after surgery, and 63.6% within 4 years.

Kumar and Thompson explain that weight regain be caused by neuroendocrine changes in regulation of metabolism that lead to a starvation response, followed by increases in appetite and energy conservation. Decreased satiety can result from loss of restriction; larger pouch size and gastrojejunal anastomosis diameter have been associated with weight regain. Gastrogastric fistula is another possible etiology. Treatment approaches for these problems include endoluminal therapy and endoscopic sutured revision of the dilated gastrojejunal anastomosis and gastric pouch.

As bariatric surgeries increase, Kumar and Thompson emphasize that it is important for gastroenterologists to become familiar with their complications and learn effective methods to address them.

Read the article online.
Kumar N, Thompson CC. Endoscopic management of complications after gastrointestinal weight loss surgery. Clin Gastroenterol Hepatol 2013;11:343–353.