Gastroesophageal reflux disease: risk factors, current possibilities of diagnosis and treatment optimisation

Gastroesophageal reflux disease (GERD) is one of the most common causes of health care seeking at the primary care level in many countries. At an epidemiological level, GERD has been shown to be associated with a number of risk factors: obesity, tobacco smoking, alcohol abuse, certain patterns of eating behaviour, and the use of several medications. GERD is now regarded as a heterogeneous disease and includes different phenotypes (erosive reflux disease, non-erosive reflux disease, hypersensitive oesophagus, functional heartburn), the proper diagnosis of which improves the effectiveness of therapy in patients with heartburn symptoms. Daily impedance–pH monitoring is known to be an integral part of the diagnostic algorithm for GERD and is a functional diagnostic method to record all types of refluxes entering the oesophagus regardless of pH, to assess their association with symptoms, and to determine whether patients with heartburn symptoms belong to a particular phenotype. Esophageal manometry plays a key role in the evaluation of patients with heartburn symptoms, as it helps to rule out other conditions that may mimic GERD: achalasia cardia and scleroderma esophagus. This technique is used to assess thoracic esophageal motility and sphincter function and in the assessment of patients prior to antireflux surgery or in the refractory course of GERD. The article describes in detail GERD risk factors (triggers of heartburn), as well as diagnostic aspects, taking into account a differentiated approach to patients with heartburn based on daily impedance–pH monitoring data in accordance with the current guidelines and recommendations

Features of the Parameters of 24-Hours pH-Impedance and High-Resolution Esophageal Manometry in Patients with Barrett's Esophagus on Proton Pump Inhibitors

Аim: to identify predictors of insufficient effectiveness of proton pump inhibitors based on the evaluation of the results of 24-hour pH-impedance and high-resolution esophageal manometry in patients with Barrett's esophagus.Materials and methods. 52 patients with histologically confirmed Barrett's esophagus who are on therapy with proton pump inhibitors were examined. All patients underwent daily pH-impedance and high-resolution esophageal manometry.Results. According to daily pH-impedance, group 1 consisted of 37 patients who responded satisfactorily to antisecretory therapy, group 2 of 15 patients who demonstrated insufficient response to acid-suppressive therapy, 11 of whom had no clinical manifestations. The total number of reflux averaged 55 in group 1 and 106 in group 2. The average number of acid reflux in group 1 was 5.68, in group 2 — 48.5. The average number of non-acid reflux prevailed in patients of group 2 and averaged 58, in group 1 the indicator averaged 47. Evaluation of the results of high-resolution esophageal manometry showed that violations of the structure and function of the esophago-gastric junction were detected in 21 patients out of 52. Disorders of the motility of the thoracic esophagus were detected in 31 patients out of 52. When comparing the frequency of motor disorders from the thoracic esophagus in groups 1 and 2, no significant differences were obtained. However, significantly more frequent registration of violations of the structure and/or function of the esophago-gastric junction was found in the group with unsatisfactory effectiveness of proton pump inhibitors.Conclusion. In a number of patients with Barrett's esophagus, there is an insufficient effect of acid-suppressive therapy and at the same time an asymptomatic course of the disease, which may increase the risk of its progression. Predictors of insufficiently successful treatment of patients with Barrett's esophagus may be both insufficient pharmacological effect of proton pump inhibitors themselves, and motility disorders that cause the presence of non-acid reflux, decreased esophageal clearance, which in turn may cause the patient's symptoms to persist and adversely affect the condition of the esophageal mucosa

High resolution manometry and new classification of esophageal motility disorders

Purpose of the review. To present application of Chicago classification criteria of esophageal motility disorders defined in high resolution manometry in clinical practice. Basic provisions. High-resolution manometry is the most exact hi-tech diagnostic method for esophageal motor function disorders according to Chicago classification v3.0. Uniqueness of the method consists in capacity to define integrated quantitative and qualitative metrics of esophageal contractile function and to establish their specific disorders e.g.: change of intrabolus pressure at disorders of esophagogastric junction (EGj) outflow, hypercontractile esophagus, fragmented contractions and weak or failed peristalsis, distal esophageal spasm. Assessment of the type of achalasia subtypes has significant impact on the patients’ treatment choice. According to anatomical location of the lower esophageal sphincter and crural diaphragm several morphological types of gastro-esophageal junction are defined that determine severity of gastroesophageal reflux disease. Multiple rapid swallow responses during esophageal high-resolution manometry reflect esophageal body peristaltic reserve and is a predictor of postoperative complications. Differential diagnosis of belching type became possible at combined application of high-resolution manometry and impedance measurement. Conclusion. High-resolution manometry is a fundamental diagnostic test of esophageal motor function disorders. Clinical application of this method significantly expands diagnostic potential and allows to carry out personalized treatment that increases treatment quality

Late pleistocene sedimentation history of the Shirshov Ridge, Bering Sea

The analysis of the lithology, grain-size distribution, clay minerals, and geochemistry of Upper Pleistocene sediments from the submarine Shirshov Ridge (Bering Sea) showed that the main source area was the Yukon–Tanana terrane of Central Alaska. The sedimentary materials were transported by the Yukon River through Beringia up to the shelf break, where they were entrained by a strong northwestward-flowing sea current. The lithological data revealed several pulses of ice-rafted debris deposition, roughly synchronous with Heinrich events, and periods of weaker bottom-current intensity. Based on the geochemical results, we distinguished intervals of an increase in paleoproductivity and extension of the oxygen minimum zone. The results suggest that there were three stages of deposition driven by glacioeustatic sea-level fluctuations and glacial cycles in Alaska

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

A Patient with Uncontrollable Belching: What to Do?

Aim. In this paper, we discuss the clinical significance of belching and present a clinical case with the description of the belching differential diagnosis.Main findings. Belching may be either a physiological or a pathological phenomenon. Pathological belching requires an adequate diagnostic approach in order to clarify the nature of its occurrence. Gastric belching occurs reflexively at the moment of stomach stretching by excess air trapped during swallowing, which initiates the transient relaxation of the lower esophageal sphincter. As a consequence, the swallowed air escapes from the stomach first into the esophagus and then into the throat. Supragastric belching is a phenomenon, in which the air entering the esophagus does not reach the stomach, but rapidly returns to the throat. In this case, unlike aerophagia, the air entering the esophagus is not accompanied by the act of swallowing. Supragastric belching is not a reflex process; rather, it is considered to be a manifestation of behavioural disorders. 24-hour pH-impedancemetry and high-resolution esophageal manometry are highly informative methods for detecting various types of belching (gastric and supragastric), as well as their mechanisms. We present a clinical observation of a 47-year-old patient suffering from supragastric belching and treated by speech therapy under the supervision of a speech therapist. Conclusion. 24-hour pH-impedancemetry and high-resolution esophageal manometry (also in combination with impedancemetry) provide a complete differential diagnosis of belching and allow the most effective patient management strategy to be selected

Indicators of Esophageal pH-Impedance Monitoring and High-Resolution Manometry in Patients with Various Forms of Gastroesophageal Reflux Disease

Aim.  The aim of the study is to analyze the regularities of changes in the basic indicators of esophageal pH-impedance monitoring and high-resolution manometry in patients with non-erosive reflux disease (NERD), erosive reflux disease (ERD) and Barrett’s esophagus (BE) in comparison with healthy individuals.Materials and methods.  69 patients were examined, including 19 patients with NERD, 16 patients with ERD, 14 patients with BE and 20 individuals comprising the control group (CG). The gender structure was as follows: 44 male and 25 female patients. The average age of the examined patients was 46 years. All patients underwent 24-hour esophageal pH-impedance monitoring and high resolution manometry.Results.  According to the data of 24-hour pH-impedance monitoring, the total time in the esophagus with pH &lt; 4 was 2.4 % in the control group, 9 % in the NERD group, 20.25 % in the ERD group and 23.5 % in the patients with BE (p &lt; 0.05). The average number of acid refluxes was 22.5 in CG, 61 in the NERD group, 77 in the ERD group and 86 in patients with BE (p &lt; 0.05). The time of chemical clearance was 1.7 minutes in CG, 2.2 minutes in the group of patients with NERD, 2.9 minutes in the ERD group and 3 minutes in the BE group (p &lt; 0.05). The mean nocturnal baseline impedance was 2483.5 Ohm in CG, 1775.0 Ohm in the NERD group, 771.0 Ohm in the ERD group and 911.0 Ohm in the BE group (p &lt; 0.05). The normal parameters of the esophagogastric junction (EGJ) structure and function according to the data of highresolution manometry were observed among 85 % of the control group, 63 % of patients with NERD, 25 % of patients with ERD and 36 % of BE group. The presence of hiatal hernia (HH) and/or hypotension of lower esophageal sphincter (LES) was observed in 15 % of patients from the CG, in 37 % of patients with NERD, in 75 % of patients with ERD and in 64 % of patients with BE. The normal parameters of the motor function of the esophagus were observed in CG (85 %), as well as in patients with NERD (79 %). In patients with ERB and BE, normal motor activity was noted in 25 % and 29 % of the cases, respectively. Disturbances of the motor function of the thoracic esophagus in CG were represented in 10 % of the cases by ineffective peristalsis and hypercontractility in the form of distal esophagospasm in 5 % of the cases. In the NERD group, 16 % of patients had ineffective peristalsis and 5 % of patients had hypercontractility in the form of a hypercontractile esophagus. In patients of ERD and BE groups, the disorders of the motor function of the thoracic esophagus were predominantly represented by ineffective peristalsis, in 75 % and 50 % of the patients, respectively. In addition, in the group of patients with BE, in 21 % of the cases, motor function disorders were observed in the form of absence of thoracic esophagus contractions.Conclusion.  It is shown that such indicators as increased level of acid exposure, increased amount of acid reflux, slowed chemical clearance, lowered mean nocturnal baseline impedance, as well as disorders in the structure and function of the esophageal-gastric junction and motility of the thoracic esophagus are associated with the severity of GERD