David C. Kunkel

Characteristics of intestinal metaplasia in the gastric cardia

OBJECTIVE:Intestinal metaplasia of the gastroesophageal junction is frequently grouped together with Barretts esophagus. The area of the gastroesophageal junction is comprised of the distal esophagus and the gastric cardia. The aim of the present study was to assess whether intestinal metaplasia in the distal esophagus and gastric cardia represent two different entities with a different set of risk factors.METHODS:Patients presenting for elective upper endoscopy were enrolled into a prospective study. The presence of gastritis and intestinal metaplasia was evaluated in gastric biopsies taken from the antrum, corpus, and cardia. Barretts esophagus was defined by the presence of any length of columnar mucosa above the gastroesophageal junction.RESULTS:Of 302 patients, 50 patients had intestinal metaplasia of the gastric cardia, 73 Barretts esophagus, and 116 erosive esophagitis. Men were more prone than women to develop Barretts esophagus or erosive esophagitis. Both conditions were also more common among whites than nonwhites. Smoking was particularly common among patients with Barretts esophagus. Patients with cardiac intestinal metaplasia did not share these demographic characteristics. The prevalence of daily reflux symptoms, erosive esophagitis, and Barretts esophagus was similar among patients both with and without cardiac intestinal metaplasia. However, atrophy and intestinal metaplasia of the gastric antrum and corpus were found more frequently among patients with than without cardiac intestinal metaplasia.CONCLUSIONS:Intestinal metaplasia of the gastric cardia is different from Barretts esophagus. Although cardiac intestinal metaplasia is closely associated with signs of gastritis in other parts of the stomach, gastroesophageal reflux disease does not seem to be a risk factor. A diagnosis of Barretts esophagus should not be made based on the presence of intestinal metaplasia within the cardiac portion of the gastroesophageal junction.

Efficacy of the glucagon‐like peptide‐1 agonist exenatide in the treatment of short bowel syndrome

Background  Short bowel syndrome (SBS) is a serious clinical disorder characterized by diarrhea and nutritional deprivation. Glucagon‐like peptide‐1 (GLP‐1) is a key hormone, produced by L‐cells in the ileum, that regulates proximal gut transit. When extensive ileal resection occurrs, as in SBS, GLP‐1 levels may be deficient. In this study, we test whether the use of GLP‐1 agonist exenatide can improve the nutritional state and intestinal symptoms of patients with SBS.

H19 Imprinting Control Region Methylation Requires an Imprinted Environment Only in the Male Germ Line

ABSTRACT The 2.4-kb H19 imprinting control region (H19ICR) is required to establish parent-of-origin-specific epigenetic marks and expression patterns at the Igf2/H19 locus. H19ICR activity is regulated by DNA methylation. The ICR is methylated in sperm but not in oocytes, and this paternal chromosome-specific methylation is maintained throughout development. We recently showed that the H19ICR can work as an ICR even when inserted into the normally nonimprinted alpha fetoprotein locus. Paternal but not maternal copies of the ICR become methylated in somatic tissue. However, the ectopic ICR remains unmethylated in sperm. To extend these findings and investigate the mechanisms that lead to methylation of the H19ICR in the male germ line, we characterized novel mouse knock-in lines. Our data confirm that the 2.4-kb element is an autonomously acting ICR whose function is not dependent on germ line methylation. Ectopic ICRs become methylated in the male germ line, but the timing of methylation is influenced by the insertion site and by additional genetic information. Our results support the idea that DNA methylation is not the primary genomic imprint and that the H19ICR insertion is sufficient to transmit parent-of-origin-dependent DNA methylation patterns independent of its methylation status in sperm.

Acute Liver Failure Following One Year of Daily Consumption of a Sugar-Free Energy Drink

We report a 36-year-old man who presented with 1 week of right upper quadrant abdominal pain, jaundice, and fatigue. He consumed 3 sugar-free energy drinks daily for the past year with binge alcohol use. His liver function progressively deteriorated, requiring orthotopic liver transplantation. Submassive hepatic necrosis with eosinophilic infiltrate was seen on pathology, consistent with drug-induced liver injury. Further investigation is warranted into identifying which individuals are susceptible to liver failure from energy drink consumption.

Successful Gastric Volvulus Reduction and Gastropexy Using a Dual Endoscope Technique

Gastric volvulus is a life threatening condition characterized by an abnormal rotation of the stomach around an axis. Although the first line treatment of this disorder is surgical, we report here a case of gastric volvulus that was endoscopically managed using a novel strategy. An 83-year-old female with a history of pancreatic cancer status postpylorus-preserving Whipple procedure presented with a cecal volvulus requiring right hemicolectomy. Postoperative imaging included a CT scan and upper GI series that showed a gastric volvulus with the antrum located above the diaphragm. An upper endoscopy was advanced through the pylorus into the duodenum and left in this position to keep the stomach under the diaphragm. A second pediatric endoscope was advanced alongside and used to complete percutaneous endoscopic gastrostomy (PEG) placement for anterior gastropexy. The patients volvulus resolved and there were no complications. From our review of the literature, the dual endoscopic technique employed here has not been previously described. Patients who are poor surgical candidates or those who do not require emergent surgery can possibly benefit the most from similar minimally invasive endoscopic procedures as described here.

Artifact Rejection Methodology Enables Continuous, Noninvasive Measurement of Gastric Myoelectric Activity in Ambulatory Subjects

The increasing prevalence of functional and motility gastrointestinal (GI) disorders is at odds with bottlenecks in their diagnosis, treatment, and follow-up. Lack of noninvasive approaches means that only specialized centers can perform objective assessment procedures. Abnormal GI muscular activity, which is coordinated by electrical slow-waves, may play a key role in symptoms. As such, the electrogastrogram (EGG), a noninvasive means to continuously monitor gastric electrical activity, can be used to inform diagnoses over broader populations. However, it is seldom used due to technical issues: inconsistent results from single-channel measurements and signal artifacts that make interpretation difficult and limit prolonged monitoring. Here, we overcome these limitations with a wearable multi-channel system and artifact removal signal processing methods. Our approach yields an increase of 0.56 in the mean correlation coefficient between EGG and the clinical “gold standard”, gastric manometry, across 11 subjects (p < 0.001). We also demonstrate this system’s usage for ambulatory monitoring, which reveals myoelectric dynamics in response to meals akin to gastric emptying patterns and circadian-related oscillations. Our approach is noninvasive, easy to administer, and has promise to widen the scope of populations with GI disorders for which clinicians can screen patients, diagnose disorders, and refine treatments objectively.