How extent of Barrett's metaplasia influences the risk of esophageal adenocarcinoma.

PURPOSE OF REVIEW: This review will focus on how the extent of Barrett's metaplasia influences the risk of esophageal adenocarcinoma (EAC). More specifically, this review will discuss the concepts of long and short-segment Barrett's metaplasia and irregular Z line as they relate to EAC risk. RECENT FINDINGS: The Prague classification can standardize reporting of Barrett's metaplasia. Recent literature has found significant associations between the length of Barrett's metaplasia and increased progression risk to EAC in multiple geographically distinct populations. Length of Barrett's metaplasia has been incorporated into the Progression of Barrett's esophagus (PIB) model that can predict individualized life-time risks of progression. The risk of malignant transformation appears to be very low in patients with irregular Z line. SUMMARY: Length of Barrett's metaplasia has emerged as an important predictor that can influence the risk of EAC and should be reported using the Prague classification. The PIB model, if further validated, could help a practicing gastroenterologist to inform patients with Barrett's metaplasia about their personal risk of progression to tailor surveillance intervals. Current guidelines do not recommend surveillance in patients with irregular Z line, but careful examination is recommended.

Outcome, complication and follow-up of patients with esophageal foreign body impaction: an academic institute's 15 years of experience.

Esophageal foreign body impaction (EFBI) is a gastrointestinal emergency, mostly requiring endoscopic management. The aim of this study is to evaluate the epidemiology, adverse events, and outcomes of patients following the episode of EFBI. All esophagogastroduodenoscopy (EGD) reports of admitted patients for EFBI at the University of Kansas Medical Center between 2003 and 2018 were retrospectively reviewed. Of 204 patients, who met the inclusion criteria, 60% were male and the mean age was 54.7 ± 17.7 years. The encounter was the first episode of EFBI in 76% of cases. EGD in less than 24 hours of patients' admission was required in 79% of cases. The distal esophagus was the most common site of impaction (44%). Push and pull techniques were used in 38 and 35.2% of cases, respectively, while 11% were managed by a combination of both techniques. Structural causes were the most common etiologic findings including benign strictures and stenosis in 21.5% of patients, followed by Schatzki's ring (7.8%) and hiatal hernia (6.9%). Of all cases, 45% did follow-up in up to 1 year, and biopsy was done in 34% of cases. Out of 43 patients who had endoscopic findings suspicious for eosinophilic esophagitis (EoE), the diagnosis was confirmed by pathology in 37. The rate of recurrence EFBI was significantly higher in patients with EoE (P < 0.001). EFBI-related esophageal adverse events (AEs) occurred in 4.9% of cases. Cardiovascular and pulmonary AEs occurred in 1.5 and 2.9%, respectively. Logistic regression did not find any predictor for AEs occurrence. EFBI managed very well with endoscopic treatments. Despite the emerging data about the safety of the push technique, there are still concerns regarding its adverse events especially the risk of perforations. Our study shows no significant difference in adverse events between different types of techniques.

Frequency of Jackhammer Esophagus as the Extreme Phenotypes of Esophageal Hypercontractility Based on the New Chicago Classification.

BACKGROUND: Jackhammer Esophagus is defined as intact esophageal peristaltic contractions with extremely elevated amplitudes. We conducted a retrospective study to identify the frequency of esophageal hypercontractility and the clinical characteristics of Jackhammer Esophagus. METHODS: Charts for the patients referred for manometric study at a tertiary-care motility center were reviewed. Data were collected utilizing the new Chicago classification criteria for Jackhammer Esophagus. Concomitant clinical variables were also explored. RESULTS: Eight patients were identified with Jackhammer Esophagus from a total of 205 (127 female/77 male) patients referred for high-resolution esophageal manometry. Jackhammer patients had an average distal contractile integral (DCI) of 9061 mmHg/ sec/ cm and median maximal DCI of 16,433 mmHg/ sec/ cm. The greatest DCI from 15 swallows was 28,875 mmHg/ sec/ cm. Hypercontractility was associated with multipeaked contractions in every Jackhammer patient. The mean lower esophageal sphincter (LES) pressure was 41 mm Hg with 4 patients having a hypertensive pressure of >40 mm Hg. Three of the 8 (37.5%) Jackhammer group had incomplete LES relaxation by integrated relaxation pressure criteria (>15 mm Hg residual pressure). Dysphagia (8/8) was the dominant indication for the manometric study, whereas the clinical background setting was gastroesophageal reflux disease (4/8) and hiatal hernia (1/8). Treatments included smooth muscle relaxation, antireflux regimens, and pneumatic dilation of the LES. CONCLUSIONS: Jackhammer Esophagus, an extreme manometric phenotype, was identified in 4.0% of patients referred to a University Motility Center. The patients with these esophageal hypercontractility states present mainly with dysphagia. A subgroup of Jackhammer did have accompanying incomplete LES relaxation and responded to targeted therapy with pneumatic dilatation.

Cyclic vomiting syndrome: treatment options.

Cyclic vomiting syndrome is a disorder characterized by recurrent episodes of severe nausea and vomiting separated by symptom-free periods. Our aims were to review treatments of adult cyclic vomiting syndrome as well as to identify areas for further clinical research and the unanswered questions in this field. We conducted a PubMed search using such keywords as "cyclic vomiting syndrome," "nausea," "vomiting," "treatment," "trigger factors" and "tricyclic antidepressants" and combined this information with the knowledge and clinical research from the authors. Available data show that in adult cyclic vomiting syndrome, there is an impressive and sustained response to high-dose tricyclic antidepressants. In up to 13% who are regarded as poor responders to tricyclic antidepressants, a predictable profile can be identified related to coexisting psychological disorders, marijuana use, poorly controlled migraine headache or chronic narcotic use. Cyclic vomiting syndrome in adults is being an increasingly recognized entity. Tricyclic antidepressants are the main treatment for controlling symptoms. Eliminating and addressing trigger factors are an essential part of management.

Prokinetics in diabetic gastroparesis.

Within the last 50 years, diabetic gastroparesis has become a well recognized complication of type 1 and type 2 diabetes. It is a syndrome characterized by abnormal gastric function, resulting in delayed emptying of the stomach in the absence of any evident mechanical obstruction, predominantly manifested by early satiety, postprandial fullness, nausea, vomiting, and weight loss. The past five years have shown significant advances in its pathophysiology and in new diagnostic tests. Prokinetic medications remain the therapeutic focus for improving clinical symptoms of gastroparesis through enhanced gastric emptying. This article summarizes the present knowledge of prokinetics, with emphasis on medications currently available, as well as drugs under clinical investigation, including some agents in advanced clinical trials that are likely to be used in the treatment of diabetic gastroparesis in the future. These include the ghrelin agonists and newer 5-HT4 agonists devoid of cardiac side effects.

Does grading the severity of gastroparesis based on scintigraphic gastric emptying predict the treatment outcome of patients with gastroparesis?

OBJECTIVES: The objectives of this study were as follows: (1) Whether gastric emptying is different between gastroparesis (GP) patients responding or not responding to standard medical therapy; (2) Identifying if mild, moderate, and severe degrees of gastroparesis based on the scintigraphic gastric emptying test (GET) can predict treatment responses for GP of diabetic (DM) and idiopathic (ID) origin. METHODS: A total of 165 patients (119 F) diagnosed with GP [126 (76%) DM, 39 (24%) ID etiology] failed medical treatment and required the gastric electrical stimulation (GES) device (GES group). In addition, 112 patients (89 F) [37 (33%) DM, 75 (67%) ID] with GP who symptomatically responded to medical therapies are the comparison group (MED GP). All patients underwent a standardized scintigraphic GET consisting of low-fat (2%) isotope labeled egg beaters meal of 250 kcal. We also analyzed the GET data to find cut-off points for different degrees of GP and identified mild (11-20% retention), moderate (21-35%), and severe gastroparesis (>35%) based on percent retention of isotope at 4 h. RESULTS: Overall gastric retention at 4 h was significantly greater in the GES group (45±1.9%) than MED GP (30±2%) (p<0.001). The distribution severity of the GET was different in GES-treated patients than MED treated (p<0.001). In the diabetics, 57% of GES patients retained >35% after 4 h (severe) similar to 43% in the DM MED group. However, 50% of the ID GES patients had retention>35% at 4 h significantly more than only 17% of ID MED GP. Significantly more ID patients who responded to medical therapy had mild gastroparesis and significantly more requiring GES had severe GET (p<0.05). CONCLUSIONS: (1) GET in patients whose GP symptoms were refractory to standard medical therapy and required GES was significantly slower than in GP patients whose symptoms responded to medical therapy. (2) Stratifying GET into mild, moderate, and severe degrees of gastric retention does not predict whether a medical or surgical approach will be better to control the symptoms of diabetic GP but does correlate with treatment for the idiopathic GP subgroup.

Efficacy of tricyclic antidepressant therapy in adults with cyclic vomiting syndrome: a two-year follow-up study.

AIM: To investigate the effects of prolonged tricyclic antidepressants (TCAs) therapy on the frequency and duration of episodes of cyclic vomiting syndrome (CVS) in adults, and the global assessment of clinical improvement and the number of emergency department (ED) visits and/or hospitalizations. METHOD: An open labeled study was conducted in adult CVS patients treated with a TCA and followed for up to 2 years. Demographic data, TCA dosage, duration and frequency of CVS episodes, ED visits, and hospitalizations at baseline and during TCA therapy were recorded, and patients were monitored for any adverse events. RESULTS: Forty-six patients initially met the inclusion criteria and 41 patients (22 male) with mean age of 35 years (range: 18 to 63 y) on TCA were able to be followed for 1 year and 23 were evaluated for 2 years. Mean age of onset of CVS symptoms was 26 years (range: 10 to 52 y) and mean age for making the diagnosis of CVS was 32 years (range: 15 to 63 y). The frequency and duration of an episode and ED visits related to CVS were all significantly reduced after both the first and second year of TCA therapy (P<0.05). Eighty-eight percent reported an improved clinical status by subjective global assessment. Mild side effects were reported in 34% not necessitating stoppage of the TCA. CONCLUSIONS: Long-term TCA therapy significantly reduces the frequency and duration of CVS episodes, ED visits, and hospitalizations (P<0.05), and improves overall clinical well-being providing evidence that they are effective therapy for adult CVS.

Dumping syndrome: establishing criteria for diagnosis and identifying new etiologies.

AIMS: To investigate the current incidence and identify the current etiologies of rapid gastric emptying (dumping syndrome) in patients with a spectrum of gastrointestinal symptoms, including nausea, vomiting, abdominal pain, or diarrhea. METHODS: The results for a 4-h radionuclide gastric emptying test (GET) using a standardized scintigraphic technique were reviewed in 545 patients to see which patients met criteria for rapid gastric emptying, defined as >50% emptying of isotope-labeled solid meal at 1 h. RESULTS: Forty-eight of 545 (8.8%) patients (28 females, mean age 46 +/- 2 years, range 32-58 years) had rapid GET. Seventeen of 59 (35%) met Rome III diagnostic criteria for cyclic vomiting syndrome (CVS). Twelve of these 59 (25%) patients were regarded as non-ulcer dyspepsia and six (13%) had dyspepsia in the setting of diabetes mellitus. Five (10.5%) were post-fundoplication surgery, where an accidental vagotomy was confirmed by sham meal challenge; previous gastric bypass surgery for obesity had been performed in three (6%) patients. Five (10.5%) patients with unexplained abdominal pain and diarrhea had the working diagnosis of irritable bowel syndrome. CONCLUSIONS: Rapid gastric emptying can be identified in a sizeable subset (9%) of patients with unexplained nausea, vomiting, abdominal pain, and diarrhea when criteria are applied to the standardized scintigraphic gastric emptying meal.

Disturbances of esophageal motility in eosinophilic esophagitis: a case series.

Esophageal manometry (EM) findings were reviewed in 14 (13 male) adults diagnosed with eosinophilic esophagitis (EE). One had complete nonperistaltic contractions (amplitude range = 30-180 mmHg) and incomplete relaxation of the lower esophageal sphincter (LES), suggesting vigorous achalasia. After 6 months of steroid therapy the repeat EM showed near-normal findings. One had total aperistalsis with contraction amplitudes less than 10 mmHg and a weak LES pressure (8 mmHg), criteria suggesting scleroderma. Two had low-amplitude (<30 mmHg) nonperistaltic contractions limited to the mid-esophagus. Criteria for nutcracker esophagus were met in two patients. Isolated low LES pressure (<15 mmHg) was observed in four patients who were also receiving proton pump inhibitors, and the remainder had normal EM findings. Our results found that EE can mimic all the categories of EM disturbances, with approximately 50% of our patients having a major impairment of smooth muscle function. The EM abnormality can be reversed to normal in some cases with appropriate treatment for EE.

Computational Fluid Dynamics (CFD)-Based Optimization of Injection Process during Endoscopic Mucosal Therapy.

Creation of a submucosal plane to separate the lesion from the deeper muscle layer in gastrointestinal tract is an integral and essential part of endoscopic resection therapies such as endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Thereby, an optimized submucosal injection technique is required to ensure a successful process. In this study, the computational fluid dynamics (CFD) technique is employed as a foundational step towards the development of a framework that can provide useful directions to optimize the injection process. Three different lifting agents, including Glycerol, Eleview®, and ORISE® gel have been used for this study. The role of different injection angles, injection dynamics, and effect of temperature are studied to understand the lifting characteristic of each agent. The study shows that Eleview® provides the highest lifting effect, including the initial injection period. To evaluate the impact of the injection process, two cases are simulated, termed static injection and dynamic injection. Under static injection, the injection angle is investigated from lower to higher angles of injection. In the dynamic injection, two cases are modulated, where a continuous change of injection angle from lower to higher degrees (denoted as clockwise) and vice-versa in the anti-clockwise direction are investigated. Increased lifting characteristics are observed at decreasing/lower angle of injection. Further, the correlation between temperature of the lifting agents and their lifting characteristics is investigated.

Gastroparesis, pseudoachalasia and impaired intestinal motility as paraneoplastic manifestations of small cell lung cancer.

Lung cancer is the worldwide leading cause of cancer deaths. Small cell lung cancer (SCLC) represents about 15% of lung cancers with a poor 5-year survival rate. SCLC can manifest as a paraneoplastic syndrome, which can include unexplained gastrointestinal dysmotility symptoms. The awareness of these presenting symptoms and recognition that serum markers, such as anti-Hu antibodies, mediate the paraneoplastic neuromuscular aspects of SCLC are highlighted in this case report of a patient with anti-Hu antibodies presenting with gastroparesis, pseudoachalasia, and impaired intestinal motility.

Epidemiological investigation of femoral fractures in market pigs and the associated economic implications.

The cause of an increased number of femoral fractures in market pigs from a single producer is described. Blood chemical, bone ash, radiographic, and feed analyses revealed that the fractures were caused by insufficient calcium in the diet. Associated economic and welfare implications are discussed.

Video Capsule Endoscopy: A Tool for the Assessment of Small Bowel Transit Time.

PURPOSE: Video capsule endoscopy (VCE) is a procedure that uses a wireless camera to take pictures of the gastrointestinal (GI) tract. A wireless motility capsule (WMC) of a similar size has been developed, which measures pH, pressure, and temperature and can be used to assess regional and total GI transit times. VCE could also potentially be used as a tool for measuring small bowel transit time (SBTT). METHODS: This study was designed to obtain SBTT from VCE and compare it with historical data generated by WMC. Gastric transit time (GTT) was also measured. Patients were included if the indication for VCE was either iron deficiency anemia (IDA) or overt obscure GI bleed (OOGIB), and they did not have any known motility disorder. Results from VCE were also compared in diabetic vs. non-diabetic patients. RESULTS: There were a total of 147 VCE studies performed, including 42 for OOGIB and 105 for IDA. Median GTT and SBTT were 0.3 and 3.6 h, respectively. The overall median GTT and SBTT were 0.3 and 3.6 h, respectively, in the IDA group compared with 0.3 and 3.4 h in the OOGIB group. When compared with WMC, the GTT and SBTT were significantly faster in both groups (GTT: 3.6 h and SBTT: 4.6 h). The median GTT and SBTT were not significantly different in diabetics vs. non-diabetics [GTT: 17.5 vs. 18.0 min (P = 0.86) and SBTT: 3.9 h (237 min) vs. 3.8 h (230 min), respectively (P = 0.90)]. CONCLUSION: SBTT as measured using VCE is not significantly different in OOGIB compared with IDA. Both GTT and SBTT are significantly faster as assessed by VCE, which is initiated in the fasting state, compared with WMC measurement, which is initiated after a standard meal. In summary, VCE could potentially be used for measuring SBTT in the fasting state.

Brainstem removal using compressed air for subsequent bovine spongiform encephalopathy testing.

The use of compressed air to expel the obex through a hole in the skull generated using a captured bolt stunner. The obex is the part of the brain that is tested for bovine spongiform encephalopathy.

Rumination syndrome: a review of current concepts and treatments.

Rumination is a normal and common phenomenon among ruminant animals; but in humans, it is always regarded as symptom indicative of abnormal function of the upper gastrointestinal tract, and understanding of the mechanisms explaining this event are still evolving. Learning-based theories, organic factors such as gastroesophageal reflux disease and psychological disturbances (eg, depression, anxiety) and the role of life stresses have been postulated as potential mechanisms of rumination. In this review, we take the approach that rumination syndrome is a distinct and discrete functional gastroduodenal disorder. We review current concepts of the pathophysiology of this entity and diagnostic approaches, then detail the treatment paradigms that have been pursued in rumination syndrome in adults. Patients with rumination syndrome have a very distinct set of symptoms. It was focused on the immediate postprandial period, but recently, there is an awareness of an expanding spectrum of the clinical presentation. This includes the concept of "conditioned vomiting" occurring in the setting of delayed gastric emptying (gastroparesis). Physicians' awareness of rumination syndrome is essential in the diagnosis and management of this disorder. Stress and psychological aspects in rumination syndrome are invariably in the background and have to be addressed. The crucial steps in the treatment strategy for rumination syndrome rely on reassurance, education and a physiologic explanation to the patient and family that this is not a "disease," followed by behavioral and relaxation programs and addressing stress factors.

Gastroesophageal reflux symptoms not responding to proton pump inhibitor: GERD, NERD, NARD, esophageal hypersensitivity or dyspepsia?

Gastroesophageal reflux (GER) is a common gastrointestinal process that can generate symptoms of heartburn and chest pain. Proton pump inhibitors (PPIs) are the gold standard for the treatment of GER; however, a substantial group of GER patients fail to respond to PPIs. In the past, it was believed that acid reflux into the esophagus causes all, or at least the majority, of symptoms attributed to GER, with both erosive esophagitis and nonerosive outcomes. However, with modern testing techniques it has been shown that, in addition to acid reflux, the reflux of nonacid gastric and duodenal contents into the esophagus may also induce GER symptoms. It remains unknown how weakly acidic or alkaline refluxate with a pH similar to a normal diet induces GER symptoms. Esophageal hypersensitivity or functional dyspepsia with superimposed heartburn may be other mechanisms of symptom generation, often completely unrelated to GER. Detailed studies investigating the pathophysiology of esophageal hypersensitivity are not conclusive, and definitions of the various disease states may overlap and are often confusing. The authors aim to clarify the pathophysiology, definition, diagnostic techniques and medical treatment of patients with heartburn symptoms who fail PPI therapy.

Nonspecific motility disorders, irritable esophagus, and chest pain.

This paper presents commentaries on whether Starling's law applies to the esophagus; whether erythromycin affects esophageal motility; the relationship between hypertensive lower esophageal sphincter and vigorous achalasia; whether ethnic- and gender-based norms affect diagnosis and treatment of esophageal motor disorders; health care and epidemiology of chest pain; whether normal pH excludes esophageal pain; the role of high-resolution manometry in noncardiac chest pain; whether pH-impedance should be included in the evaluation of noncardiac chest pain; whether there are there alternative therapeutic options to PPI for treating noncardiac chest pain; and the usefulness of psychological treatment and alternative medicine in noncardiac chest pain.