Recent advances in diagnostic testing for gastroesophageal reflux disease.

INTRODUCTION: Gastroesophageal reflux disease (GERD) has a large economic burden with important complications that include esophagitis, Barrett's esophagus, and adenocarcinoma. Despite endoscopy, validated patient questionnaires, and traditional ambulatory pH monitoring, the diagnosis of GERD continues to be challenging. Areas covered: This review will explore the difficulties in diagnosing GERD with a focus on new developments, ranging from basic fundamental changes (histology and immunohistochemistry) to direct patient care (narrow-band imaging, impedance, and response to anti-reflux surgery). We searched PubMed using the noted keywords. We included data from full-text articles published in English. Further relevant articles were identified from the reference lists of review articles. Expert commentary: Important advances in novel parameters in intraluminal impedance monitoring such as baseline impedance monitoring has created some insight into alternative diagnostic strategies in GERD. Recent advances in endoscopic assessment of esophageal epithelial integrity via mucosal impedance measurement is questioning the paradigm of prolonged ambulatory testing for GERD. The future of reflux diagnosis may very well be without the need for currently employed technologies and could be as simple as assessing changes in epithelia integrity as a surrogate marker for GERD. However, future studies must validate such an approach.

Novel insights into esophageal diagnostic procedures.

The 21st century offers new advances in diagnostic procedures and protocols in the management of esophageal diseases. This review highlights the most recent advances in esophageal diagnostic technologies, including clinical applications of novel endoscopic devices, such as ultrathin endoscopy and confocal laser endomicroscopy for diagnosis and management of Barrett's esophagus; novel parameters and protocols in high-resolution esophageal manometry for the identification and better classification of motility abnormalities; innovative connections between esophageal motility disorder diagnosis and detection of gastroesophageal reflux disease (GERD); impedance-pH testing for detecting the various GERD phenotypes; performance of distensibility testing for better pathophysiological knowledge of the esophagus and other gastrointestinal abnormalities; and a modern view of positron emission tomography scanning in metastatic disease detection in the era of accountability as a model for examining other new technologies. We now have better tools than ever for the detection of esophageal diseases and disorders, and emerging data are helping to define how well these tools change management and provide value to clinicians. This review features novel insights from multidisciplinary perspectives, including both surgical and medical perspectives, into these new tools, and it offers guidance on the use of novel technologies in clinical practice and future directions for research.

Impact of laparoscopic antireflux surgery on belching in pediatric GERD patients.

BACKGROUND: Laparoscopic antireflux surgery (LARS) is a well-established treatment option for children with proton pomp inhibitor (PPI)-resistant gastroesophageal reflux disease (GERD). Besides preventing reflux of gastric fluid and solid content, LARS may also impair the ability of the stomach to vent intragastric air (i.e. gastric belching) and induce gas-related complications, such as bloating and/or hyperflatulence. Furthermore, it was previously hypothesized that LARS induces a behavioral type of belching, not originating from the stomach, called supragastric belching. The aim of this study was to objectively evaluate the impact of LARS on gastric (GB) and supragastric belching (SGB) in children with GERD. METHODS: We performed a prospective, Dutch multicenter cohort study including 25 patients (12 males, median age 6 (range 2-18) years) with PPI-resistant GERD who were scheduled for LARS. Twenty-four-hour multichannel intraluminal impedance pH monitoring (MII-pH monitoring) was performed before and 3 months after fundoplication. Impedance pH tracings were analyzed for reflux episodes and GBs and SGBs. KEY RESULTS: LARS reduced acid exposure time from 8.5% (6.0-16.2%) to 0.8% (0.2-2.8%), p < 0.001. The number of GBs also significantly decreased after LARS (59 [43-77] VS 5 [2-12], p < 0.001). The number of air swallows remained unchanged after LARS. SGBs were infrequent before LARS with no change in the number of SGB observed after the procedure. Postoperative belching symptoms were associated with GBs, not with SGBs. CONCLUSION & INFERENCES: LARS significantly reduces the number of GBs in children with GERD, whereas the number of air swallows remains unchanged. Postoperative symptomatic belching is associated with GBs, but not with SGBs. These findings suggest that LARS does not induce the occurrence of SGBs in children, but longer follow-up is required.

Proton pump inhibitor-responsive esophageal eosinophilia: a historical perspective on a novel and evolving entity / Esofagitis eosinofílica respondedora a los inhibidores de la bomba de protones: perspectiva histórica sobre una entidad nueva y en desarrollo

Eosinophilic esophagitis (EoE) is an emerging chronic esophageal disease, first described in 1993, with a steadily increasing incidence and prevalence in western countries. Over the 80´s and early 90´s, dense esophageal eosinophilia was mostly associated gastroesophageal reflux disease (GERD). For the next 15 years, EoE and GERD were rigidly considered separate entities: Esophageal eosinophilia with pathological acid exposure on pH monitoring or response to proton pump inhibitor (PPI) therapy was GERD, whereas normal pH monitoring or absence of response to PPIs was EoE. Updated guidelines in 2011 described a novel phenotype, proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE), referring to patients who appear to have EoE clinically, but who achieve complete remission after PPI therapy. Currently, PPI-REE must be formally excluded before diagnosing EoE, since 30-40 % of patients with suspected EoE are eventually diagnosed with PPI-REE. Interestingly, PPI-REE and EoE remain undistinguishable based on clinical, endoscopic, and histological findings, pH monitoring, and measurement of tissue markers and cytokines related to eosinophilic inflammation. This review article aims to revisit the relatively novel concept of PPI-REE from a historical perspective, given the strong belief that only GERD, as an acid peptic disorder, could respond to the acid suppressing ability of PPI therapy, is becoming outdated. Evolving evidence suggests that PPI-REE is genetically and phenotypically undistinguishable from EoE and PPI therapy alone can almost completely reverse allergic inflammation. As such, PPI-REE might constitute a subphenotype of EoE and PPI therapy may be the first therapeutic step and diet/ steroids may represent step up therapy. Possibly, the term PPI-REE will be soon replaced by PPIresponsive EoE. The mechanism as to why some patients respond to PPI therapy (PPI-REE) while others do not (EoE), remains to be elucidated

Impedanciometría esofágica multicanal y pHmetría en el estudio del episodio de riesgo vital aparente del lactante / Esophageal multichannel intraluminal impedance and pH-testing in the study of apparent life threatening episode incidents in infants

Introducción: la pHmetría convencional de 24 horas constituye el patrón de oro para el diagnóstico de episodios de riesgo vital aparente (ALTE). La impedanciometría intraluminal multicanal (IIM) puede aportar ventajas en el lactante. Objetivos: comparación de los resultados de IIM y pHmetría en los pacientes sometidos a IIM-pHmetría en el periodo de estudio por causa de estudio de ALTE. Material y métodos: estudio retrospectivo de IIM-pHmetrías realizadas en nuestro servicio a lactantes < 12 meses de edad ingresados por ALTE durante tres años. Resultados: 39 pacientes estudiados. La pHmetría registró 2.692 reflujos, con medianas de 24 (IQ: 15-44) reflujos/paciente, índice de reflujo de 1,30 (IQ: 0,80-2,60) reflujos/hora, 1 (IQ: 0-4) episodio de reflujo > 5 min por paciente y aclaramiento de 1,20 (IQ: 0,70-2,20) min/reflujo. Por pHmetría 14 niños (35,9 %) fueron diagnosticados de RGE. Mediante IIM se registraron 8.895 eventos; 3.219 fueron reflujos, con mediana de 75 (IQ: 54-111) reflujos/ paciente, 1,30 (IQ: 1,3-2,6) reflujos/hora. Mediante IIM-pHmetría, la media de reflujos ácidos por paciente fue de 21,60 (DE 15,21), débilmente ácidos 67,33 (DE 32,09) y no ácidos 3,34 (DE 7,23), pudiéndose diagnosticar finalmente a 33 pacientes de RGE. Conclusiones: la asociación de IMM y pHmetría proporciona información adicional que mejora el rendimiento diagnóstico, sin suponer ningún riesgo adicional para el paciente. Los reflujos no ácidos/débilmente ácidos, los cuales no son detectados mediante pHmetría, suponen un porcentaje elevado, sobre todo en lactantes; esto tiene gran importancia diagnóstica en el estudio del ALTE. Aún son necesarios estudios para valorar la normalidad en IIM en pacientes pediátricos (AU)

Introduction: The conventional 24-hour pH monitoring is the gold standard for the diagnosis of gastro-esophageal reflux (GER), a possible cause of Apparent Life Threatening Episodes (ALTE). However, multichannel intraluminal impedance (MII) may provide advantages. Objectives: Comparison of the results of MII and pH monitoring in patients undergoing MII-pH monitoring in the 3-year study period because of having suffered from ALTE. Material and methods: Prospective study of MII-pH monitoring performed in our unit to infants < 12 months of age admitted for ALTE for a 3-year period. Results: Thirty nine patients studied. 2,692 pH monitoring episodes, with median of 24 (IQ: 15-44) episodes/patient, 1.30 (IQ: 0.80-2.60) reflux/hour, 1 (IQ: 0-4) reflux episode > 5 min per patient and clearance of 1.20 (IQ: 0.70-2.20) min/reflux. With pH monitoring analysis, 14 children (35.9 %) could have been diagnosed as GER (8 mild, 4 moderate and 2 severe) based on the classical criteria. MII identified a total of 8,895 events; only 3,219 among them were refluxes, with a median of 75 (IQ: 54-111) per patient, 1.30 (IQ: 1.3-2.6) episodes/hour). With MII-pH monitoring combination there were 21.60 (SD 15.21) acid reflux episodes, 67.33 weekly acid (SD 32.09) and 3.34 (SD 7.23) non-acid, being finally diagnosed 33 patients as GER. Conclusions: The association of pH monitoring and MII provides additional information that improves GER diagnostic performance without posing any additional risk to the infant patient. The non-acid/weekly acid refluxes, not detected by pH monitoring, account for a high percentage of episodes, this may have diagnostic and therapeutic significance, especially in infants. Further studies are needed to assess the normality of MMI in pediatric patients (AU)

Advances in motility testing--current and novel approaches.

Disorders of gastrointestinal motility are frequently seen in clinical practice. Apart from motility disorders, factors leading to lowered visceroperception thresholds are recognized as commonly involved in the pathogenesis of functional gastrointestinal disorders. The wide array of gastrointestinal motility and viscerosensitivity tests available is in contrast with the relatively limited number of tests used universally in clinical practice. The main reason for this discrepancy is that the outcome of a test only becomes truly important when it carries clinical consequences. The main goal of this Review is to assess the place of the presently available gastrointestinal motility and sensitivity tests in the clinical armamentarium of the gastroenterologist.

Advancements in the analysis of esophageal pH monitoring in GERD.

Ambulatory 24 h esophageal pH monitoring enables quantification of esophageal acid exposure and assessment of the temporal relationship between symptoms and acid reflux events. Analysis of pH monitoring is currently divided into upright and recumbent periods based on the patient's body position. However, in this Review, we demonstrate that physiologic studies have shown that sleep, and not recumbency, has a greater impact on gastroesophageal reflux during night-time. The physiologic studies are further supported by clinical trials demonstrating that gastroesophageal reflux characteristics during the recumbent-awake period are similar to those in the upright rather than the recumbent-asleep period. The introduction of the integrated pH monitoring and actigraphy data analysis program offers better separation of the recumbent-awake and recumbent-asleep periods. The physiologic studies and clinical trials, as well as the availability of a better tool to measure pH during sleep, support a paradigm shift in the analysis of pH monitoring data from body position (upright or recumbent) to state of consciousness (awake or asleep).

Does an upper gastrointestinal study change operative management for gastroesophageal reflux?

BACKGROUND: In patients with gastroesophageal reflux disease, an upper gastrointestinal (UGI) contrast study is often the initial study performed for those patients being considered for fundoplication. The accuracy of UGI for diagnosing reflux is known to be poor, but there are no data on how often this study influences management. Therefore, we reviewed our experience in patients undergoing fundoplication to quantify the impact of the UGI. METHODS: A retrospective analysis of our most recent 7-year experience with patients undergoing fundoplication was performed. Results of the diagnostic tests and operative course were recorded. RESULTS: From January 2000 to June 2007, 843 patients underwent fundoplication. An UGI study was obtained in 656 patients. A pH study was also performed in 379 of these patients who had an UGI. The sensitivity of the UGI for reflux compared with pH study was 30.8%. An abnormality besides gastroesophageal reflux disease or hiatal hernia that impacted the operative plan was found on the UGI in 30 patients (4.5%). The most common anomaly was malrotation, which was found in 26 patients (4.0%). Malrotation was confirmed in 16 patients and ruled out in 6 patients during fundoplication, and 4 patients had undergone a previous Ladd procedure. Esophageal dilation was performed in 5 patients with the fundoplication for a stricture found on the UGI. Pyloroplasty was performed with the fundoplication in 2 patients, and 1 patient underwent exploration of the duodenum for possible obstruction. CONCLUSIONS: The UGI study is a poor study for accurately delineating which patients have pathologic reflux. However, it reveals a finding that may influence management in approximately 4% of cases.

Valores normales en pHmetría esofágica ambulatoria a dos niveles en España / No disponible

Objetivo: la pHmetría con electrodo proximal puede jugar unpapel importante en el estudio de las manifestaciones extraesofágicasde la ERGE, pero no existen series amplias que permitan establecerlos valores de referencia con fiabilidad.Métodos: se incluyeron 155 voluntarios sanos (74 H) en unestudio multicéntrico a nivel nacional con manometría esofágica ypHmetría de 24 horas con dos electrodos individuales a 5 cm porencima del borde superior del EEI y a 3 cm por debajo del bordeinferior del EES.Resultados: completaron todos los estudios 130 sujetos. Sedesestimaron 12 por pHmetrías deficientes y 27 por presentaruna pHmetría patológica en el esófago distal. Los 91 voluntariosrestantes –37 H; media de edad: 28,5 años (rango 18-72)– constituyeronel grupo de referencia para valores de normalidad. A niveldel esófago superior el percentil 95 del número total de episodiosfue 30, al eliminar los periodos de ingesta 22, y al eliminarademás los seudo-reflujos 18. Los valores para la duración delepisodio más largo fueron 5, 4 y 4 min (3,5 min en bipedestacióny 0,5 min en decúbito), respectivamente. El límite superior para el% de tiempo de exposición ácida fue de 1,35, 1,05 y 0,95%,igual respectivamente. No se registraron episodios de reflujo en elesófago superior en 8 casos (17 al eliminar el periodo de ingestao los seudo-reflujos).Conclusión: esta es la serie más amplia de valores normalesde reflujo en el esófago proximal, con datos de referencia a nivelde la población española que confirman la existencia de reflujoácido a ese nivel en sujetos sanos, de escasa cuantía y sin relacióncon la edad o sexo. Nuestros resultados apoyan la convenienciade eliminar los seudo-reflujos y periodos de ingesta en el análisis(AU)

Aim: upper oesophageal pH monitoring may play a significantrole in the study of extra-oesophageal GERD, but limitednormal data are available to date. Our aim was to develop a largeseries of normal values of proximal oesophageal acidification.Methods: 155 healthy volunteers (74 male) participated in amulti-centre national study including oesophageal manometry and24 hours oesophageal pH monitoring using two electrodes individuallylocated 5 cm above the LOS and 3 cm below the UOS.Results: 130 participants with normal manometry completedall the study. Twelve of them were excluded for inadequate pHtests. Twenty-seven subjects had abnormal conventional pH. Theremaining 91 subjects (37 M; 18-72 yrs age range) formed the referencegroup for normality. At the level of the upper oesophagus,the 95th percentile of the total number of reflux events was30, after eliminating the meal periods 22, and after eliminatingalso the pseudo-reflux events 18. Duration of the longest episodeswas 5, 4 and 4 min, respectively (3.5 min in upright and 0.5 minin supine). The upper limit for the percentage of acid exposuretime was 1.35, 1.05 and 0.95%, respectively. No reflux eventswere recorded in the upper oesophagus in 8 cases.Conclusion: this is the largest series of normal values of proximaloesophageal reflux that confirm the existence of acid refluxat that level in healthy subjects, in small quantity and unrelated toage or gender. Our data support the convenience of excludingpseudo-reflux events and meal periods from analysis(AU)

Impedance-pH monitoring: new standard for measuring gastro-oesophageal reflux.

Impedance monitoring is a new technique that can be used to detect the flow of fluids and gas through hollow viscera. With impedance monitoring gastro-oesophageal reflux can be detected independent of its acidity by differences in electrical impedance between the mucosal surface, fluids and gas that surround the catheter. Clinically, it is used in combination with oesophageal pH monitoring, and the combination of impedance-pH monitoring allows recognition of both acidic and weakly acidic reflux episodes. Studies have shown that impedance-pH monitoring is useful in the evaluation of patients with proton pump inhibitor-resistant typical reflux symptoms, as it provides a higher yield in detecting reflux as the cause of a patient's symptoms compared to pH monitoring alone. It is therefore likely that impedance-pH monitoring will largely replace pH monitoring in the next 5 years and it will become the standard for reflux detection.

Enfermedad por reflujo gastroesofágico: epidemiología, diagnóstico y tratamiento / Gastroesophageal reflux disease: epidemiology, diagnosis and treatment

Entre las novedades del año 2006 en la enfermedad por reflujo gastroesofágico (ERGE), destaca la confirmación de que la obesidad y, en particular, la acumulación de grasa visceral son factores de riesgo de primer orden para la aparición de reflujo gastroesofágico. El mecanismo principal de esta asociación parece ser el aumento del gradiente de presión entre la luz gástrica y la esofágica. Se presentaron también datos sobre el efecto favorable de la cirugía bariátrica basada en bypass gastrointestinal sobre el reflujo gastroesofágico. Desde el punto de vista diagnóstico, destaca tanto la evidencia creciente de la utilidad de la impedanciometría esofágica para el diagnóstico de ERGE (que amplía las posibilidades de estudio más allá del reflujo ácido), como algunas propuestas para mejorar el diagnóstico del reflujo ácido. Así, la asociación de impedanciometría y pHmetría puede detectar, entre los pacientes que no responden al tratamiento estándar con inhibidores de la bomba de protones, una proporción importante con reflujo gastroesofágico no ácido como causa de los síntomas. Esto posibilita nuevos enfoques para el abordaje clínico de la ERGE en la práctica diaria como la selección individualizada del tratamiento farmacológico o quirúrgico. Finalmente, hay que destacar la notable evolución de las nuevas técnicas para el tratamiento endoscópico de la ERGE y del esófago de Barrett (AU)

Among the advances made in 2006 in gastroesophageal reflux disease (GERD), notable was the confirmation that obesity and, in particular, the accumulation of visceral fat are major risk factors for the development of gastroesophageal reflux. The main mechanism for this association seems to be an increase in the pressure gradient between the gastric and the esophageal lumen. Data were also presented on the beneficial effect of bariatric surgery based on gastrointestinal bypass on gastroesophageal reflux. From the diagnostic point of view, both the growing evidence of the utility of impedancometry in the diagnosis of GERD (increasing the possibilities of study beyond acid reflux) and other proposals to improve the diagnosis of acid reflux were also of great interest. Thus, in nonresponders to standard treatment with protein pump inhibitors, the association of impedancometry and pH monitoring can detect a substantial proportion with nonacid gastroesophageal reflux as a cause of the symptoms. This allows a new focus in the clinical approach to GERD in daily clinical practice, such as individualized selection of drugs or surgery. Finally, new techniques for the endoscopic treatment of GERD and Barrett’s esophagus have undergone considerable development (AU)

Ambulatory esophageal pH monitoring: new directions.

pH testing remains a commonly used evaluative tool in clinical practice. However, the original tool that included a nasally placed pH catheter was plagued with a variety of shortcomings, primarily the effect of the procedure on patients' lifestyle and thus on reflux-provoking activities. The miniaturization of evaluative techniques in gastroenterology was the impetus for the development of the wireless pH capsule and the SmartPill. These modalities improve patients' tolerability of the required test and provide a unique opportunity for expansion of indications and data collection. The introduction of the multichannel intraluminal impedance with a pH sensor allowed the detection of gastroesophageal reflux that is non-acidic. However, the value of the technique beyond the realm of academic gastroenterology remains to be elucidated. Recently, there was a renewal of interest in Bilitec 2000. The technique, which has never found a clear clinical role, has been recommended as an important tool in evaluating patients who failed proton pump inhibitor therapy. However, data to support its clinical value in this situation have remained scant.